Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

Novotná, Martina; Soldán, M. Mateo Paz; Zeid, Nuhad Abou; Kale, Nilüfer; Tütüncü, Melih; Crusan, Daniel J.; Atkinson, Elizabeth J.; Síva, Aksel; Keegan, B. Mark; Pirko, Istvan; Pittock, Sean J.; Lucchinetti, Claudia F.; Noseworthy, John H.; Weinshenker, Brian G.; Rodriguez, Moses; Kantarci, Orhun H.

doi:10.1212/wnl.0000000000001856

Cited by 88 publications

(73 citation statements)

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“…Acute exacerbations in MS are associated with a high risk of incomplete remission resulting in increased disability [4,5] . We observed functional improvement in 71.4% of patients shortly after the IA series.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that a marked proportion of relapses is followed by incomplete recovery resulting in a residual increase in Expanded Disability Status Scale (EDSS) [4] . Poor recovery from early relapses led to considerably earlier onset of progressive MS than good relapse recovery [5] . Therefore, efficient therapies to treat acute MS exacerbations are of particular importance.…”

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confidence: 95%

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Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

et al. 2016

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Background: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. Methods: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. Results: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. Conclusion: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

et al. 2016

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“…The mean time to progression to SSPM was 30.2 years in half of the patients with relapses recovered fully or close to fully within the first 5 years, whereas this period was 8.3 years in poor recoverers (43).…”

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confidence: 89%

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

Sevim¹

2016

tnd

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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...

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“…Of patients who did not improve with first-line treatment, the majority improved with second-line immunotherapy, most often rituximab or cyclophosphamide [20]. Judging from the experience with other autoimmune brain disorders, such as multiple sclerosis [76], an even more favorable outcome may be likely if the immunological attack is milder, resulting only in psychotic symptoms.…”

Section: Synaptic Autoimmunity Against the Nmdar In Humansmentioning

confidence: 99%

NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?

Masdeu

Dalmau

Berman

2016

Trends in Neurosciences

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Since the early 1990s it has been postulated that hypofunction of N-methyl-D-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. Here we review this mechanism as well as data supporting or refuting the possibility that this disorder, or similar autoimmune disorders affecting synaptic proteins which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.

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Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

Abstract: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

Cited by 88 publications

References 44 publications

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients

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

NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?

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