Primary progressive multiple sclerosis

Thompson, Alan

doi:10.1093/brain/120.6.1085

Cited by 388 publications

(236 citation statements)

References 2 publications

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“…However, axonal damage and loss also occur in MS 15,16 and may contribute to persistent and progressively increasing disability. 17 Antiganglioside antibodies could possibly play a role in axonal damage. Convincing evidence that immune responses against gangliosides can be pathogenic has been provided by the induction of experimental sensory ataxic neuropathy in rabbits by immunization with GD1b 18 .…”

Section: Discussionmentioning

confidence: 99%

Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis

Sadatipour

Greer

Pender

1998

Annals of Neurology

127

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Plasma samples from 70 patients with multiple sclerosis (MS), 41 patients with other neurological diseases (OND), and 38 healthy subjects were examined for anti-bodies against gangliosides GM1, GM3, GDla, GD1b, and GD3 using enzyme-linked immunosorbent assays. The percentages of subjects with increased anti-GM3 responses were significantly higher in the primary progressive MS (56.3%) and secondary progressive MS (42.9%) groups than in the relapsing-remitting MS (2.9%), healthy subject (2.6%), and OND (14.6%) groups. Elevated antiganglioside antibodies may be secondary to axonal damage or may be a cause of axonal damage and accumulating disability in progressive MS. In either case, they may serve as a marker of axonal damage in MS.Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Typically MS initially has a relapsing-remitting (RR) course; however, often this relapsing-remitting course eventually changes to a progressive one (secondary progressive [SP] MS). In 10 to 20% of cases of MS, the disease has a progressive course from onset (primary progressive [PP] MS). The cause of MS is unclear, but there is increasing evidence that it is an autoimmune disease. 1,2 Because primary demyelination is a characteristic pathological feature of MS, myelin components, particularly myelin proteins, are considered to be the likely target antigens. 1,2 Recently we have shown that patients with RRMS or SPMS, but not PPMS, have increased peripheral blood T-cell proliferative responses to a region of myelin proteolipid protein ) that is encephalitogenic in mice. 3 The lack of an increased Tcell response to this region of PLP in PPMS raises the possibility that the main target antigens in PPMS are not myelin antigens, but axonal antigens. 4 An immune attack directed primarily at axonal antigens could explain the progressive course of this form of MS, as the capacity for CNS axonal regeneration is much more limited than the capacity for CNS remyelination, which is likely to contribute to the recovery from attacks of RRMS. The transition from RRMS to SPMS could involve the spreading of the immune response from myelin to axonal antigens. 4 Gangliosides constitute an important group of axonal antigens and are also minor constituents of myelin. A number of studies have found increased amounts of antiganglioside antibodies in the sera or cerebrospinal fluid (CSF) of patients with MS compared with healthy subjects. [5][6][7][8][9][10][11][12] However, the significance of this is unclear, because in most studies the antiganglioside levels in MS patients were not compared with those in patients with OND 6,9,12 or, if they were compared, were not significantly different. 7,11 The only study that has compared antiganglioside antibody levels among the RR, SP, and PP forms of MS is that of Acarin and colleagues. 12 They found elevated serum antibodies against GM1, asialoGM1, and GDla significantly more frequently in PPMS than in RRMS or SPMS; however, the number of patients wit...

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Section: Discussionmentioning

confidence: 99%

Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis

Sadatipour

Greer

Pender

1998

Annals of Neurology

127

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“…7,8 A diagnosis of laboratory supported definite primary progressive MS can be made when there is evidence of intrathecal immunoglobulin synthesis, a progressive neurological course and evidence of at least two separate lesions developing at different times. In the absence of evidence of intrathecal immunoglobulin synthesis, some would argue that a diagnosis of clinically definite primary progressive MS can be made if there is disease progression and symptoms and neurological signs of two separate lesions commencing at least one month apart, with the possibility of MRI or electrophysiological symptoms, of a second lesion.…”

Section: *From Lublin and Reingoldmentioning

confidence: 99%

“…3 it is not possible to make a diagnosis of clinically definite primary progressive MS because the criteria require the presence of at least two discrete attacks, which by definition do not occur in primary progressive MS. 8 The diagnostic difficulty in primary progressive MS is compounded by the fact that brain MRI may be normal in this form of MS when there are multiple visible lesions in the spinal cord, 9 and by the fact that MRI brain lesions not due to MS are more frequent in the older age group in which primary progressive MS tends to occur. 7 At present it is often difficult to exclude confidently all other diseases that may mimic primary progressive MS. There is, therefore, a need to define the diagnostic criteria of primary progressive MS more precisely; this is particularly important for therapeutic trials, as currently there is a paucity of reliable information concerning the treatment of primary progressive MS.…”

Section: *From Lublin and Reingoldmentioning

confidence: 99%

Recent progress in the diagnosis and treatment of multiple sclerosis

Pender

1999

Journal of Clinical Neuroscience

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Magnetic resonance imaging (MRI) now provides valuable diagnostic and prognostic information for the management of multiple sclerosis (MS) but the diagnosis still largely rests on the clinical features of central nervous system (CNS) lesions disseminated in time and place. Recent histological and MRI studies indicate that extensive axonal damage can occur in MS, even early in the disease course, and is likely to be an important cause of accumulating disability. Several immunomodulating agents have now been shown to have beneficial effects in MS. High dose intravenous or high dose oral methylprednisolone therapy accelerates recovery from attacks of relapsing-remitting MS, but at present there is no convincing evidence that standard dose (intermediate dose) oral corticosteroid therapy is beneficial for such attacks. Interferon beta, copolymer 1 (glatiramer acetate) and i.v. immunoglobulin therapy each significantly reduce the frequency of attacks of relapsing-remitting MS. Interferon beta also inhibits the progression of disability in relapsing-remitting MS and secondary progressive MS, but its effect on primary progressive MS is unknown. Oral low dose methotrexate therapy slows the progression of disability in secondary progressive MS and possibly in primary progressive MS, but it is likely that the currently used dosage (7.5 mg weekly) is suboptimal. Further research is needed to determine the optimal doses and combinations of the above therapies in MS and to develop better therapies, particularly for primary progressive MS.

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“…Men also have a higher frequency of primary progressive and lower frequency of bout-onset (relapsing-remitting and secondary progressive) disease course compared to women. 25 Pelfrey et al 26 demonstrated that PLP-induced IFNg secretion was higher in women than men in both patients with MS and controls. The percentage of IFNg-producing CD3 cells correlates with disease severity in women but not in men.…”

Section: Introductionmentioning

confidence: 99%

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

et al. 2005

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Interferon-gamma (IFNg) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNg expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1 (761)

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Primary progressive multiple sclerosis

Cited by 388 publications

References 2 publications

Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis

Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis

Recent progress in the diagnosis and treatment of multiple sclerosis

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

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