Magnetic resonance imaging of spinal cord lesions in multiple sclerosis.

The clinical and pathological manifestations of multiple sclerosis are due to areas of demyelination which occur throughout the white matter of the central nervous system. MRI of the brain frequently shows abnormalities in the hemispheric subcortical white matter; these are demonstrable in the majority of patients and support the clinical diagnosis of multiple sclerosis. Our studies have shown that while MRI identifies such cerebral lesions in nearly all clinically definite multiple sclerosis patients with illness of duration greater than 10 years, these areas of abnormal T2 signal are present less often in the brains of patients studied within 3 years of disease onset. However, symptoms referable to the long tracts of the spinal cord are prominent in many of these patients. Imaging of the spinal cord has presented technical problems because of the small size of the cord, patient body, heart and respiratory movements, and limitations of surface coil technology. The spinal cord of 77 patients with multiple sclerosis have been imaged, revealing three types of abnormalities: (1) approximately half the cords show regions of abnormal T2 weighted signal; (2) during acute exacerbation, spinal cord enlargement (swelling) may be observed; (3) spinal cord atrophy (narrowing) is found particularly in patients with disease of longer duration and greater disability. Unlike the presence of brain lesions, the existence of spinal cord lesions of high T2 signal is not associated with increasing duration of disease but is correlated with disability status. Of patients with such lesions about one fifth did not exhibit brain lesions discernible by MRI.     

Demyelinating lesions in cervical spinal cord and disability in multiple sclerosis patients

BACKGROUND AND PURPOSE: In multiple sclerosis (MS) lesions appear both in brain and cervical cord. The aim of this study was to estimate the presence of MRI changes in cervical cord depending on the course, duration of the disease and a disability. MATERIAL AND METHODS: Clinical measures included 66 patients suffering from MS, the diagnosis was made according to McDonald's criteria. Patients were aged from 18 to 62 (41 women and 25 men). RESULTS: In patients with relapsing-remitting form (EDSS 1-4) single lesions were seen whereas secondary progressive patients (EDSS 3-7) had diffuse demyelinating lesions and primary progressive patients (EDSS 4-8)--both kinds of changes. It has been shown that the lesions occurred as the disease proceeds. Patients without demyelinating lesions in cervical cord had EDSS from 1 to 3 and the duration of their disease was longer than 10 years (benign MS). CONCLUSIONS: The duration of the disease depends on the presence and character of demyelinating lesions in cervical cord to a large extent. That dependence was not noticed in a primary progressive form. In benign MS there were no lesions in cervical cord.     

Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions

To investigate remyelination in multiple sclerosis lesions, we immunostained spinal cord sections from patients with multiple sclerosis and neurological normal (control) patients with antisera to P0 protein, a major constituent of peripheral nervous system myelin, and myelin basic protein, which is found in both central and peripheral nervous system myelin. In sections from five of the eight patients with no clinical or pathological evidence of neurological disease, P0 immunostaining was confined to peripheral myelin sheaths in dorsal and ventral roots. They were intensely stained, and peripheral--central nervous system transition zones were clearly demarcated. Sections from the other three control patients contained a few P0-stained sheaths in the central nervous system near root entry zones or among marginal glia near the dorsal sulcus. Spinal cord sections from six of the ten patients with multiple sclerosis contained clusters of myelin sheaths immunostained by P0 antiserum. These regenerating sheaths of peripheral nervous system origin were most numerous in large lesions and were commonly located in central areas or peripherally near root entry zones. The sheaths were observed frequently in areas of active demyelination and appeared morphologically normal even when surrounded by debris-filled macrophages. Near margins of small inactive plaques were a few basic protein--stained oligodendroglia extending processes to thin basic protein--stained sheaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal cord lesions of multiple sclerosis

The neuropathological findings of the spinal cord lesions of six human multiple sclerosis cases are described. The spinal cord was extensively necrotic and occasionally cystic in five remitting and relapsing cases. The lesions became more severe as the disease course prolonged and relapses increased. The spinal cords of two cases in particular, with a duration of illness of more than 5 years, were severely atrophic. In these cases, peripheral type remyelination was prominent, although central type remyelination was minimal. In contrast, in mouse spinal cords, in which experimental demyelination and remyelination were induced by ethidium bromide, the degree of central type remyelination and peripheral type remyelination was almost the same. Longitudinal sections of the transitional zone between the areas of central type remyelination and peripheral type remyelination contrained Ranvier nodes, in which central type myelin and peripheral type myelin were situated side by side around a central type axon. These transitional zones were similar to those of the normal transitional zone between the central nervous system and peripheral nervous system of the nerve roots. One chronic progressive case, despite the very long duration of illness, showed classical sharply demarcated demyelinated lesions with marked fibrillary gliosis. The spinal cord of this case was not atrophic and axons were well preserved.     

Extensive extracellular matrix depositions in active multiple sclerosis lesions

In the central nervous system, basement membrane (BM) constituents are predominantly associated with the vasculature. However, under inflammatory conditions, the expression of BM components may alter. Here, we investigated the distribution of several BM components, including laminin, collagen type IV and heparan sulfate proteoglycans in various multiple sclerosis (MS) lesions. We observed irregular and discontinuous BMs in active lesions. Throughout active MS lesions, we found dense networks of BM proteins, which were surprisingly not associated with the cerebrovasculature. These striking parenchymal networks were not observed in chronic inactive MS lesions and brains of non-neurological controls. In addition, we studied the distribution of transforming growth factor-beta1 (TGF-beta1), since it is known as a major modulator of ECM production. Leukocytes, in particular CD68-positive macrophages, expressed high levels of TGF-beta1 and were located in close proximity to parenchymal BM deposits in the MS lesions. We postulate that these BM networks may play a role in the further recruitment of inflammatory cells and form a barrier for axonal regeneration.     

Anti-aquaporin 4 antibody in Japanese multiple sclerosis with long spinal cord lesions]

Multiple sclerosis (MS) in Asian populations is often characterized by the selective involvement of the optic nerve (ON) and spinal cord (SP) (OSMS) in contrast to classic MS (CMS), where frequent lesions are observed in the cerebrum, cerebellum, or brainstem, as well as in the ON and SP. In Western countries, inflammatory demyelinating disease preferentially involves the ON and SP is called neuromyelitis optica (NMO). Recently, Lennon et al. have reported that NMO-immunoglobulin G (NMO-IgG), which has been shown to bind to aquaporin 4 (AQP4), could be a specific marker of the NMO. To examine the epidemiological and clinical spectra of Japanese MS with this antibody, we established an immunohistochemical detection system for the AQP4-Ab using the AQP4-transfected human embryonic kidney cell line (HEK-293) and confirmed AQP4-Ab positivity together with the immunohistochemical staining pattern of NMO-IgG in approximately 60% of Japanese MS patients with long spinal cord lesions extending over three vertebral segments (LCL (+) MS). Patients with OSMS without LCL and those with classic MS were negative for this antibody. AQP4 is totally lost in the OSMS lesions. The AQP4-Ab titer correlates with the activity of the disease and the symptom improves after plasma exchange. These results suggested the close relation to the pathogenesis of AQP4-Ab to NMO/OSMS.     

Magnetic resonance imaging in multiple sclerosis: investigation of brain and spinal cord lesions

Magnetic resonance imaging (MRI) of the brain was performed on forty-five patients with multiple sclerosis (MS), using T1-weighted inversion recovery and T2-weighted spin echo images, and the results were compared with X-ray computed tomography (CT). Some of the 45 MS patients were also examined by neurophysiological studies (visual evoked potentials and auditory brainstem responses) to compare with the brain MRI findings. MRI showed demyelinating plaques of the brain in 20 (74%) of 27 patients with brain symptoms, 11 (61%) of 18 patients without symptoms and 31 (69%) of all 45 patients. In 27 patients with brain symptoms, MRI was able to detect brain lesions in 6 (86%) of 7 acute stage patients and 14 (70%) of 20 non-acute stage patients. Furthermore, MRI was able to detect brain lesions in 21 (70%) of 30 clinically definite MS patients and 10 (67%) of 15 clinically probable MS patients. X-ray CT was performed on all 45 patients and was able to detect brain lesions in 9 (33%) of 27 patients with brain symptoms and 1 (6%) of 18 patients without symptoms. Visual evoked potentials were evaluated in 31 patients, and showed abnormalities in 1 (11%) of 9 patients without symptoms of optic neuritis and 100% of 22 patients with symptoms. Auditory brainstem responses were evaluated in 19 patients, and showed abnormalities in 1 (11%) of 9 patients without brainstem symptoms and 3 (30%) of 10 patients with symptoms. MRI of the brain was markedly superior to X-ray CT, visual evoked potentials and auditory brainstem responses in detecting clinically unsuspected lesions.(ABSTRACT TRUNCATED AT 250 WORDS)     

脊髓型多发性硬化临床诊断分析

目的 总结分析脊髓型多发性硬化(MS)的临床特点和MRI表现.方法 回顾性分析21例脊髓型MS的临床特点和MRI表现,所有患者行脊髓和颅脑MRI检查.结果 脊髓型MS除有脊髓病变的临床表现外,临床症状和体征的多样性是其特点,如感觉障碍、肢体无力、视力障碍等;脊髓内病灶的MRI特点是不规则斑片状和条带状异常信号,位于脊髓两侧和后部,在T:WI像上为高或稍高信号,在T1WI上为等信号或稍低信号;80.9%(17/21)脊髓型MS合并脑内病灶.结论 脊髓型MS临床表现呈多样性,MRI可以准确显示脊髓内病灶,颅脑MRI检查有助于脊髓型MS的诊断.     

Anti-aquaporin 4 antibody in selected Japanese multiple sclerosis patients with long spinal cord lesions

Multiple sclerosis (MS) in Asian populations is often characterized by the selective involvement of the optic nerve (ON) and spinal cord (SP) (OSMS) in contrast to classic MS (CMS), where frequent lesions are observed in the cerebrum, cerebellum or brainstem. In Western countries, inflammatory demyelinating disease preferentially involving the ON and SP is called neuromyelitis optica (NMO). Recently, Lennon et al. discovered that NMO-IgG, shown to bind to aquaporin 4 (AQP4), could be a specific marker of NMO and also of Japanese OSMS whose clinical features were identical to NMO having long spinal cord lesions extending over three vertebral segments (LCL). To examine this antibody in larger populations of Japanese OSMS patients in order to know its epidemiological and clinical spectra, we established an immunohistochemical detection system for the anti-AQP4 antibody (AQP4-Ab) using the AQP4-transfected human embryonic kidney cell line (HEK-293) and confirmed AQP4-Ab positivity together with the immunohistochemical staining pattern of NMO-IgG in approximately 60% of Japanese OSMS patients with LCL. Patients with OSMS without LCL and those with CMS were negative for this antibody. Our results accorded with those of Lennon et al. suggest that Japanese OSMS with LCL may have an underlying pathogenesis in common with NMO.     

Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody

Background

Anti‐aquaporin 4 (AQP4) antibodies were found in patients with neuromyelitis optica (NMO) and Japanese optic–spinal multiple sclerosis (OSMS).

Objective

To review the clinical features and investigate anti‐AQP4 antibodies of Japanese patients with multiple sclerosis (MS), with or without long spinal cord lesions (LCL).

Methods

Anti‐AQP4 antibodies were examined in the sera of 128 consecutive Japanese patients by the immunofluorescence method using AQP4 transfected cells.

Results

The 45 LCL‐MS patients included 28 with a long spinal cord lesion extending contiguously over three vertebral segments on sagittal T2 weighted images (long T2 lesion) and 17 with segmental cord atrophy extending more than three vertebral segments. We identified 25 patients with anti‐AQP4 antibody with LCL and anti‐AQP4 antibody. Anti‐AQP4 antibody was found in 12/17 (70.6%) LCL‐MS patients with segmental cord atrophy, and in 13/28 (46.4%) LCL‐MS patients without segmental long cord atrophy (p = 0.135, Fisher''s exact test). Seropositive MS patients with LCL had more relapses than seronegative patients (p = 0.0004, Mann–Whitney U test). 9 patients with OSMS were negative for anti‐AQP4 antibody who did not show LCL.

Conclusion

These results suggest that an anti‐AQP4 antibody is found not only in MS patients with long T2 lesions but also in patients with segmental cord atrophy extending more than three vertebral segments. It is a marker of LCL‐MS showing frequent exacerbations. Japanese OSMS cases comprised those that were identical to NMO cases and those that were more closely related to classic MS.Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system. Japanese MS patients have been classified into two phenotypes: classic MS (CMS) and optic–spinal MS (OSMS).¹ OSMS has been recognised since the 1950s.² Patients with OSMS have symptoms and MRI findings in which the main lesions are confined to the optic nerve and spinal cord. In patients with OSMS, there is a higher female/male ratio; neuropathologically necrotic lesions; pleocytosis with a predominance of polymorphonuclear cells and a low frequency of oligoclonal IgG bands in CSF; a high incidence of autoantibodies in sera; long spinal cord lesions (LCL) extending more than three vertebral segments in MRI scans; and an association with a human leucocyte antigen class II allele (DPB1*0502).³Neuromyelitis optica (NMO) has been described as Devic disease, but its clinical definition has frequently been revised.⁴ LCL extending contiguously over three vertebral segments on sagittal T2 weighted images (long T2 lesion) is a disease marker. Current NMO criteria include unilateral optic neuritis, no restriction on onset of optic neuritis and myelitis, relapsing course and brain involvement.^4,5 Recent NMO criteria stress the presence of both brain MRI abnormalities that do not meet diagnostic criteria for MS and NMO‐IgG,⁴ a highly specific biomarker of NMO,⁶ and its target antigen is the aquaporin 4 (AQP4) water channel.⁷The incidence of NMO‐IgG seropositivity in Japanese patients with OSMS (6/11 cases, 54%) was similar to that in NMO (33/45, 73%), and OSMS was thought to be the same disease.⁶ However, in that study,⁶ the Japanese OSMS patients had been selected using 1999 NMO criteria (Fujihara K, personal communication) that are not the same as the clinical definition of OSMS widely used in Japan.⁸ Their recent report showed that serum NMO‐IgG was found in 12 of 19 patients with OSMS (63%).⁹ We established an AQP4 antibody assay system and identified nine seropositive MS patients with LCL‐MS.¹⁰     

Brain and spinal cord atrophy in multiple sclerosis

Until recently, atrophy of the brain and spinal chord was thought to occur late in the course of multiple sclerosis (MS) or as a result of rare, fulminant disease. Now atrophy is known to occur early and likely indicates destructive and irreversible pathologic change that may be subclinical. Central nervous system atrophy from MS now can be measured accurately over short time intervals. Atrophy may become an important prognostic indicator in MS and is being evaluated as a treatment outcome measure in population studies, and possibly in the future, in individuals.     

T cell responses to myelin basic protein in patients with spinal cord injury and multiple sclerosis.

Autoimmune inflammation secondary to myelin destruction may play an inhibitory role in restoration of nerve functions in spinal cord injury (SCI). In this study, we demonstrated that T cells recognizing myelin basic protein (MBP) occurred at a high precursor frequency in patients with SCI, which was compatible to that in patients with multiple sclerosis (MS), a disease of presumed autoimmune pathology. The findings suggest of hyperactivity of MBP-reactive T cells in patients with SCI. MBP-reactive T cell lines derived from patients with SCI exhibited a preferential recognition pattern toward the 81-99 and the 151-169 regions of MBP. There were functional differences in the epitope recognition and cytokine profile between two panels of MBP-reactive T cell lines derived from patients with SCI and patients with MS. The study provides new evidence important for further investigation of the role of the inflammatory component in SCI.     

脊髓型多发性硬化的MRI表现

目的总结分析脊髓型多发性硬化的MRI表现。方法搜集经临床证实的脊髓型多发性硬化11例,均行MRI检查,对其临床及MRI资料进行回顾性分析。结果脊髓型多发性硬化的特征性MRI表现为,11例患者的病灶以颈髓多见,病变脊髓在T1WI像为低或等信号,T2WI像为高信号,病灶位于脊髓两侧和后部,病灶活动期呈斑片状或边缘强化,应用糖皮质激素试验性治疗对脊髓出现的可疑脱髓鞘病灶者有一定的帮助。结论脊髓型多发性硬化有其特征性MRI表现,MRI有助于脊髓型多发性硬化的诊断,是目前诊断脊髓型多发性硬化最敏感的影像学方法 。