Author response: Menarche, pregnancies, and breastfeeding do not modify long-term prognosis in multiple sclerosis

Background and Objective The presence of lipid-specific immunoglobulin M bands in the cerebrospinal fluid (CSF) predicts an aggressive course in patients with relapsing–remitting multiple sclerosis (MS) during early stages of the disease. This study examined whether it is also a predictor of long-term prognosis in MS. Methods Eighty-one patients with MS and 22 headache controls were analyzed for anti-lipid IgM reactivity in CSF samples. The correlation between the presence of lipid-specific immunoglobulin M bands in CSF and disease progression was assessed in patients with MS who had been followed longitudinally for, on average, more than 11 years. Results Lipid-specific immunoglobulin M bands were detected in the CSF of 24 of 81 patients with MS and were absent in the CSF of all headache controls. Median time to conversion to a secondary progressive course was 11 years in patients with bands and 22 years in patients without bands. Median time to an Expanded Disability Status Scale score of 4 was 14 years in patients with bands and 24 years in patients without bands. Conclusion The presence of lipid-specific immunoglobulin M bands in CSF predicts a more adverse long-term outcome in patients with MS; it may thus define a subset of patients who might benefit from aggressive treatment during the early phase of the disease.

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Onset of secondary progression and long-term prognosis in multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2013.07.1399 ◽

2013 ◽

Vol 333 ◽

pp. e385

Author(s):

A. Scalfari ◽

A. Neuhaus ◽

M. Daumer ◽

P. Muraro ◽

G. Ebers

Keyword(s):

Multiple Sclerosis ◽

Long Term Prognosis

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Axons, Cells, and Depression: The Nexus of Neurology and Psychiatry in Multiple Sclerosis

CNS Spectrums ◽

10.1017/s1092852900022689 ◽

2005 ◽

Vol 10 (5) ◽

pp. 349-350

Author(s):

Jack M. Gorman ◽

Jennifer Finkel

Keyword(s):

Multiple Sclerosis ◽

Genetic Basis ◽

Mendelian Disease ◽

Functional Impairments ◽

Fluid Analysis ◽

Long Term Prognosis ◽

Fear And Anxiety ◽

Neuroimaging Techniques ◽

Autoimmune Etiology

In many ways, multiple sclerosis (MS) is among the most frustrating and vicious of human diseases. Although we can readily see the demyelinating effect of MS lesions on postmortem examination, the diagnosis during life is fraught with difficulty. Advances in cerebrospinal fluid analysis and neuroimaging techniques have contributed to a recent revision of diagnostic criteria for MS, yet the majority of patients still wait for years until a definitive diagnosis is reached. They then face a disease that is both highly unpredictable and, in most cases, severely debilitating.The unpredictable nature of MS is particularly distressing and many patients exist in a persistent state of fear and anxiety about their next MS exacerbation. Despite improved treatments, MS leaves some of the most severely affected patients wheelchair-bound by their early twenties. The more fortunate ones learn to deal with sporadic functional impairments for the rest of their lives. The unpredictable nature of MS leaves its victims always wondering about the next phase of their illness. For some, a more negative but definitive prognosis would be easier to accept than one for which the outcome is so unclear.To make matters worse, the cause of MS remains an elusive one. Research points to an infectious and/or autoimmune etiology. The disorder is more common among those living in northern hemispheres, afflicts women more often than men, and has a partial genetic basis as evidenced by a greater concordance rate for monozygotic than dizygotic twins that nevertheless, falls far short of what would be expected of an autosomal, Mendelian disease. Drugs that modulate the immune system, from steroids to interferons, are somewhat helpful. Yet despite this, the long-term prognosis for MS has not changed much in recent decades and no therapy exists that addresses the root pathophysiology of the disease—demyelination.

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Neurofilament in CSF—A biomarker of disease activity and long-term prognosis in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458516658560 ◽

2016 ◽

Vol 22 (9) ◽

pp. 1112-1113 ◽

Cited By ~ 10

Author(s):

Per Soelberg Sorensen ◽

Finn Sellebjerg

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Long Term Prognosis

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Factors associated with and long-term outcome of benign multiple sclerosis: a nationwide cohort study

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319913 ◽

2019 ◽

Vol 90 (7) ◽

pp. 761-767 ◽

Cited By ~ 5

Author(s):

Loes Crielaard ◽

Andrius Kavaliunas ◽

Ryan Ramanujam ◽

Tomas Olsson ◽

Jan Hillert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Term Outcome ◽

Long Term Outcome ◽

Factors Associated ◽

Risk Alleles ◽

First Relapse ◽

Benign Multiple Sclerosis ◽

Edss Score ◽

Long Term Prognosis

ObjectiveBenign multiple sclerosis (BMS) is often defined by the Expanded Disability Status Scale (EDSS) score of ≤3.0 after ≥15 years of disease duration. This classification’s clinical relevance remains unclear as benign patients may suffer other impairments and advance towards a progressive course, prompting our objective to holistically investigate factors associated with BMS and its long-term prognosis.MethodsBenign cases were identified in the Swedish Multiple Sclerosis registry. Baseline clinical data, demographic features and influence of multiple sclerosis (MS) major risk alleles on likelihood of benign course were investigated. Physical disability (EDSS), cognitive function (Symbol Digit Modalities Test; SDMT) and self-reported and socioeconomic differences between benign and non-benign patients were evaluated using generalised estimation equations models.Results11222 patients (2420 benign/8802 non-benign) were included. Benign patients were more likely to be female and younger at MS onset, have fewer relapses within the first two and 5 years from onset and fully recover from the first relapse (p<0.001). No association between human leucocyte antigen (HLA) DRB1*15:01 carriership (OR: 0.97, 95% CI: 0.86 to 1.09) or HLA-A*02:01 lacking (OR: 0.99, 95% CI: 0.87 to 1.11) and benign/non-benign was found. Non-benign patients accumulated an extra 0.04 (95% CI 0.03 to 0.04, p<0.001) EDSS score/year, lost an extra 0.3 (95% CI − 0.39 to − 0.18, p<0.001) SDMT score/year and deteriorated faster in self-reported impact and socioeconomic measures (p<0.001).ConclusionPatients with BMS have a better disease course as they progress more slowly at the group level in all respects. Lack of an association with major genetic risk factors indicates that MS course is most likely influenced by either environmental factor(s) or genetic factors outside the HLA region.

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Sex effects across the lifespan in women with multiple sclerosis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420936166 ◽

2020 ◽

Vol 13 ◽

pp. 175628642093616 ◽

Cited By ~ 3

Author(s):

Kristen M. Krysko ◽

Jennifer S. Graves ◽

Ruth Dobson ◽

Ayse Altintas ◽

Maria Pia Amato ◽

...

Keyword(s):

Multiple Sclerosis ◽

Management Strategies ◽

Central Nervous System Disorder ◽

Disability Progression ◽

Sex Effects ◽

Disease Modifying Therapy ◽

Susceptibility Effects ◽

Long Term Prognosis ◽

System Disorder

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

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