The pathophysiology of multiple sclerosis⋮ the mechanisms underlying the production of symptoms and the natural history of the disease

Smith, Kenneth J.; McDonald, W. I.

doi:10.1098/rstb.1999.0510

Cited by 288 publications

(192 citation statements)

References 245 publications

(269 reference statements)

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…Consequently, conduction blocks and significant reductions in conduction velocity occur, and classic MS symptoms emerge. According to another hypothesis, formed autoantibodies adhere to Na channels, which makes the axolemma non-excitable and causes conduction block (13). Demyelination areas should have a minimum diameter of 4 mm for the formation of conduction blocks in humans.…”

Section: The Pathophysiology Of Relapse and Symptomsmentioning

confidence: 99%

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

Sevim¹

2016

tnd

View full text Add to dashboard Cite

Relapse in multiple sclerosis (MS) is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS) form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the first 3 months after birth. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed. Keywords: Multiple sclerosis, relapse, definition, features, treatmentMultipl sklerozda (MS) ateş ve enfeksiyon yokken en az 24 saat süren akut enflamatuvar demiyelinizan süreçle uyumlu nörolojik defisitler atak olarak tanımlanır. Ataklarda miyelin yıkımı ve aksonal transeksiyon oluşur. Hastalığın tanısı, seyri, tedavisi ve diğer birçok özelliği ataklarla doğrudan ilişkilidir. MS hastaların %85'inde atak ve düzelmelerle giden formda başlar. İlk yıllarda atak sayısının fazla olması, atakların birden çok semptomla ortaya çıkması, motor sistemi içermesi, beyin sapı ya da spinal atak formunda olması kötü prognoz göstergeleridir. Atak ve düzelmelerle giden formun başlangıç yıllarında yıllık ortalama atak sayısı 1'dir.Sistemik enfeksiyonlar, psişik stres ve postpartum 3 aylık dönemde atak sıklığı artar. Atakların %75'i monosemptomatiktir. Yalancı ataklar ve paroksismal bulgular genellikle ani başlayıp ani sonlanmalarıyla ve kısa sürmeleriyle ataklardan ayrılır. Görüntülemede kontrast tutulumu değerlidir, ancak atakların çoğunda saptanamaz. Ataklarda ilk birkaç hafta içindeki düzelme ödem etkisinin azalması...

show abstract

Section: The Pathophysiology Of Relapse and Symptomsmentioning

confidence: 99%

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

Sevim¹

2016

tnd

View full text Add to dashboard Cite

show abstract

“…At the onset of optic neuritis, inflammation, demyelination, and conduction block in the optic nerve occur. 38 Therefore, the amplitude of the a-wave, b-wave, and PhNR might be reduced at the onset of optic neuritis. However, over subsequent weeks, inflammation resolves and electrical conduction improves, although there is significant evidence for persistent optic nerve demyelination.…”

Section: Change In the Focal Macular Phnr After Steroid Therapymentioning

confidence: 99%

Focal macular photopic negative response in patients with optic neuritis

Nakamura

Miyamoto

Yokota

et al. 2011

Eye

View full text Add to dashboard Cite

Purpose To investigate, by focal macular electroretinography (ERG), the change of photopic negative response (PhNR) in the recovery of visual function in patients with optic neuritis. Methods Focal macular ERG was recorded from nine patients with acute optic neuritis (38.6±10.2 years). The photostimulator device projected 151 visual angle spotlight onto the macula. Focal macular ERG recording was performed at the onset and at 1 month and 6 months after the onset of optic neuritis. The results were compared between each recording for seven of the patients. Results All patients decreased in the vision below 20/100 and had central scotoma. Vision improved more than 20/20 within 1 month and full-visual field recovered within 6 months after the onset in all patients. The amplitude of the a-wave, b-wave, and PhNR of focal macular ERG at the onset was significantly attenuated in eyes with optic neuritis (66.8±15.5, 65.8±17.7, and 65.2±14.4% of normal control, respectively). The amplitude of the a-wave and b-wave increased gradually after steroid pulse therapy. The increase in a-wave amplitude was significant at 6 months (P ¼ 0.046), whereas the PhNR amplitude did not show any significant change over 6 months after the onset of optic neuritis. Conclusions Our results suggest that inflammation at the onset of optic neuritis leads to functional deficits that extend to at least the inner nuclear layers of the retina, and that all but the ganglion cell layers of retina recover.

show abstract

“…Although endogenous RM can occur in patients with MS, as evidenced by shadow plaques, it is short-lived, incomplete, and relatively ineffective (2). Transition to progressive MS is characterized by increased axon loss, which correlates with RM failure (3).…”

mentioning

confidence: 99%

Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis

Moore¹,

Khalaj

Kumar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Currently available immunomodulatory therapies do not stop the pathogenesis underlying multiple sclerosis (MS) and are only partially effective in preventing the onset of permanent disability in patients with MS. Identifying a drug that stimulates endogenous remyelination and/or minimizes axonal degeneration would reduce the rate and degree of disease progression. Here, the effects of the highly selective estrogen receptor (ER) β agonist indazole chloride (Ind-Cl) on functional remyelination in chronic experimental autoimmune encephalomyelitis (EAE) mice were investigated by assessing pathologic, functional, and behavioral consequences of both prophylactic and therapeutic (peak EAE) treatment with Ind-Cl. Peripheral cytokines from autoantigen-stimulated splenocytes were measured, and central nervous system infiltration by immune cells, axon health, and myelination were assessed by immunohistochemistry and electron microscopy. Therapeutic Ind-Cl improved clinical disease and rotorod performance and also decreased peripheral Th1 cytokines and reactive astrocytes, activated microglia, and T cells in brains of EAE mice. Increased callosal myelination and mature oligodendrocytes correlated with improved callosal conduction and refractoriness. Therapeutic Ind-Cl-induced remyelination was independent of its effects on the immune system, as Ind-Cl increased remyelination within the cuprizone diet-induced demyelinating model. We conclude that Ind-Cl is a refined pharmacologic agent capable of stimulating functionally relevant endogenous myelination, with important implications for progressive MS treatment.M ultiple sclerosis (MS) is an autoimmune, demyelinating, and neurodegenerative disease of the central nervous system (CNS) that affects 2-2.5 million people worldwide. Currently approved MS drugs reduce relapse rates but fail to reverse or prevent neurodegeneration and disability progression. Disease-modifying drugs capable of restoring neuronal function via axon remyelination (RM) represent a major unmet goal for MS therapeutics.Oligodendrocyte (OL) progenitor cells (OPCs) are responsible for remyelinating axons, make up at least 3% of all white matter cells, and are present in and around MS lesions; however, they remain largely quiescent in the adult CNS (1). Although endogenous RM can occur in patients with MS, as evidenced by shadow plaques, it is short-lived, incomplete, and relatively ineffective (2). Transition to progressive MS is characterized by increased axon loss, which correlates with RM failure (3). Hence, a treatment that stimulates endogenous OPCs to differentiate and remyelinate axons would reduce axon degeneration and restore neuronal function.Experimental autoimmune encephalomyelitis (EAE) affords researchers an in-depth, mechanistic understanding of immunemediated, demyelinating neurodegeneration and anti-inflammatory effects of currently approved MS drugs. Our recent work has demonstrated promising neuroprotective effects of the estrogen receptor (ER) β agonist 2,3-bis(4-hydroxyphenyl)propionitrile...

show abstract

The pathophysiology of multiple sclerosis⋮ the mechanisms underlying the production of symptoms and the natural history of the disease

Cited by 288 publications

References 245 publications

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

Focal macular photopic negative response in patients with optic neuritis

Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis

Contact Info

Product

Resources

About