multiple sclerosis (MS); includes clinically isolated syndrome
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Etiology
- hypotheses
- autoimmune disease directed against:
- myelin-specific proteins
- oligodendroglia
- chronic viral infection of the central nervous system
- Epstein-Barr virus (EBV)[12]
- risk of multiple sclerosis increases 32-fold after infection with EBV but remains unchanged after other viral infections[104]
- Epstein-Barr virus (EBV)[12]
- intestinal microbial flora might influence development of disease
- chronic cerebrospinal venous insufficiency is not a cause[37]
- autoimmune disease directed against:
- genetic & environmental factors contribute to susceptibility
- sunlight & vitamin D independent risk factors[26] (both protective)
- maternal vitamin D deficiency duing pregnancy associated with increased risk of multiple sclerosis in offsrping[66]
- higher serum vitamin D in the neonatal period is associated with reduced risk for multiple sclerosis years later[70]
- higher physical activity of women at baseline weakly associated with lower risk for multiple sclerosis (MS)[68]
- may be due to women reducing physical activity in response to subclinical MS[68]
- women with serum 25-hydroxyvitamin D levels < 12 ng/mL with 43% higher risk of multiple sclerosis within 9 years than those with levels > 20 ng/mL[75]
- risk highest in smokers with HLA-DRB1*1 allele exposed to organic solvents[88]
Epidemiology
- more common as distance from equator increases
- outbreaks suggest transmission of agent that induces MS
- susceptibility depends upon childhood residence
- moving during childhood from a low to a high prevalence geographic region increases risk[3]
- age of onset: 20-40 years
- genetic factors
- high prevalence in whites (90-95% of patients)
- female:male ratio 3:1
- ~ 15% of patients have a family history
- increased incidence among family members
| relationship | risk |
|---|---|
| general Caucasian population | <0.2% |
| sibling or parent with MS | 1-3% |
| dizygotic twin with MS | 2-5% |
| monozygotic twin with MS | 17-40% |
Pathology
- inflammation & demyelination
- inflammatory compromise of demyelinated axonal pathways
- IL4I1 may diminish inflammation & enhance re-myelination in multiple sclerosis[77]
- involvement of:
- optic nerve (optic neuritis)
- oculomotor nerve
- hemispheric white matter
- cerebral cortex involvement is secondary & subtle[3]
- cerebellum
- brain stem
- pyramidal tract
- vestibular pathways
- spinal cord - sensory pathways (myelitis)
- degenerative changes in both white matter & gray matter subsequent to demyelination[3]
- activation of microglia & astrocytes within the substantia nigra may be associated with fatigue in MS[96]
- demyelination of different areas of the CNS occur at different times[3]
- reduced plasma amyloid beta & reduced Alzheimer disease risk[118]
Genetics
- increased expression of syncytin-1
- other implicated genes
- no genetic markers distinguish patients with MS from unaffected identical twins[23]
Clinical manifestations
- presentation
- 85% of patients present with an attack (symptomatic episode)
- risk of 2nd attack in MRI-confirmed multiple sclerosis is 90% over next 10-15 years[3]
- symptoms originating from different parts of the central nervous system occuring as discrete episodes separated by >= 30 days
- late onset >= 50 years[115]
- more likely to have progressive disease at onset
- more likely to reach higher disability milestones
- disease patterns
- 85% have a relapsing/remitting course
- symptoms usually begin focally or unilaterally, worsening over a few days
- recovery occurs over weeks to months with recoveries becoming less complete with repeated relapses
- symptoms eventually become bilateral, disseminated, & progressive, mean time 10-15 years[3]
- 10-20% have a primary progressive course
- without exacerbations or remissions
- spinal cord often involved
- 2/3 of patients with relapsing-remitting form eventually convert to secondary progressive form over a period of 10-15 years[3]
- 10-30% have a benign course
- optic neuritis & myelitis
- 85% have a relapsing/remitting course
- common manifestations
- sensory manifestations
- numbness
- patchy sensory loss
- paresthesias: may be associated with neck flexion (Lhermitte's sign)
- pain
- weakness:
- asymmetric weakness
- most commonly in legs
- upper motor neuron pattern
- cerebellar ataxia
- gait ataxia
- decreased hand dexterity
- intention tremor
- abnormal reflexes
- hyperreflexia
- positive Babinski's sign
- spasticity[3]
- slurred speech, scanning speech, dysarthria
- visual manifestations
- ocular manifestations
- pale optic disks
- internuclear ophthalmoplegia
- nystagmus
- pain with eye movements (optic neuritis)[3]
- vertigo
- urinary urgency & incontinence
- constipation
- impotence
- depression, increased risk of suicide[3]
- diurnal fatigue (mental & physical)
- cool extremities
- heat intolerance (Uhthoff phenomenon)
- worsening of symptoms with activity or heat
- fever
- cognitive impairment[3]
- sensory manifestations
- less common manifestations
- rare manifestations
- symptoms may be vague, preceding objective signs
- clinically isolated syndromes of the cerebrum, optic nerve, or brainstem & cerebellum without sign/symptoms of spinal cord disease[35]
- pregnancy
- fertility is normal
- disease activity generally declines during pregnancy, but often relapses within 2 months postpartum
- overall course of the disease is unaffected by 1 or more pregnancies
Diagnostic criteria
- objective abnormalities in the CNS, i.e. positive MRI
- involvement of white matter long tracts:
- involvement of 2 or more areas of the CNS
- dissemination in time & space
- 2 or more episodes of symptoms involving 2 different site in the CNS, each lasting at least 24 hours & occurring at least 1 month apart
- no longer required
- symptomatic spinal cord or brainstem lesions count[81]
- stepwise progression over 6 months & at least 2 CSF IgG oligoclonal bands
- elevated CSF IgG index
- 2 or more episodes of symptoms involving 2 different site in the CNS, each lasting at least 24 hours & occurring at least 1 month apart
- age of onset 15-60 years
- condition not attributable to another disease[3][45]
* patients with clinically isolated syndrome (full criteria for MS not met) but with brain lesions on MRI have ~90% 10 year risk of developing MS[3]
Laboratory
- confirmatory testing
- cerebrospinal fluid (not necessary but helpful)[3]; important[111]
- CSF protein electrophoresis
- serum protein electrophoresis as a control
- oligoclonal bands in CSF, but not in serum (oligoclonal bands in serum&CSF)
- IgG index > 0.70 [CSF (IgG/albumin)/serum (IgG/albumin)]
- cell count: < 40 WBC/mm3, predominantly lymphocytes
- CSF protein < 100 mg/dL
- CSF protein electrophoresis
- cerebrospinal fluid (not necessary but helpful)[3]; important[111]
- exclusion testing
- serum 25-hydroxyvitamin D
- higher serum 25-hydroxyvitamin D diminishes risk
- serum 25-hydroxyvitamin D > 20 ng/mL during the 1st year of MS associated with slower 5 year progression[47][117]
- less frequent relapses & fewer newer MRI lesions in patients with higher serum 25-hydroxyvitamin D levels[3]
- serum 25-hydroxyvitamin D levels are inversely associated with MS activity on brain MRI[60]
- myelin-oligodendrocyte glycoprotein IgG in serum/plasma[111]
- aquaporin 4 receptor IgG in serum/plasma[111]
- CRYAB antibody in CSF
- 2-fold increase in methionine sulfoxide in CSF[78]
- assessment of subclinical disease activity
- neurofilament light chain in serum levels is significantly higher in patients with MRI-confirmed subclinical disease activity[79]
- serum neurofilament light (NfL), a marker of axonal injury, predicts both relapse-associated worsening & disease progression independent of relapse[119]
- serum GFAP is a better indicator of MS disease progression than serum neurofilament light chain[108]
- see ARUP consult[32]
Diagnostic procedures
- visual evoked potentials
- ophthalmoscopy: optic disk pallor consistent with optic neuritis
- optic coherence tomography[111]
- measurement of central conduction velocities after visual, auditory & somatosensory stimuli
- neuropsychologic testing
- transcranial sonography
- substantia nigra changes may predict risk for progression
Radiology
- magnetic resonance imaging with gadolinium enhancement
- diagnosis with MRI prior to treatment
- imaging of brain & spinal cord
- high intensity area on T2-weighted scans involving CNS white matter
- a confirmatory MRI must have 4 lesions involving white matter, or 3 if one is periventricular
- newer criteria invoke dissemination in space[25]
- >= 2 T2 lesions in typical MS locations[25]
- juxtacortical, periventricular, infratentorial spinal cord
- one lesion must enhance with gadolinium, another must not enhance (1st MRI)
- a new T2 lesion identified >= 30 days after a prior scan
- >= 2 T2 lesions in typical MS locations[25]
- rule out lesion compressing spinal cord, brainstem
- lesions generally ovoid in shape & periventricular in distribution[3]
- enhancement with gadolinium suggests acute disease, non-enhancing lesions suggest older asymptomatic lesions[3]
* diabetes mellitus, hypercholesterolemia, hypertension, migraine, & smoking may cause T2 hyperintensities on MRI as well as demyelinating disease[69]
Complications
- disease interaction(s) of multiple sclerosis with obesity
- disease interaction(s) of multiple sclerosis with type-2 diabetes
- disease interaction(s) of multiple sclerosis with COVID-19
- disease interaction(s) of multiple sclerosis with urinary incontinence
Differential diagnosis
- migraine (22%)*
- fibromyalgia (15%)*
- other demyelinating diseases
- acute disseminated encephalomyelitis (ADEM)
- Devic's disease (neuromyelitis optica) (6%)*
- spinal cord lesions longitudinal rather than segmental in MS
- lack of significant brain involvement
- profound CSF leukocytosis
- idiopathic transverse myelitis
- optic neuritis[111]
- somatoform disorders[3]
- conversion disorder or other psychogenic disorder (11%)*
- autoimmune disorders
- infections
- Lyme disease (Borrelia burgdorferi)
- tertiary syphilis
- human T-cell lymphotropic virus-1 (HTLV-1)
- HIV myelopathy or HIV-related cerebritis
- mitochondrial myopathy
- sarcoidosis
- adult-onset leukodystrophy
- adrenoleukodystrophy
- metachromatic leukodystrophy
- non-specific white matter changes[100]
- metabolic disorders
- vascular disorders
- spinocerebellar degeneration
- paraneoplastic syndrome[3]
- brain neoplasms
- structural lesions
- craniocervical junction tumor or malformation
- base of skull anomaly
- posterior fossa tumor or arteriovenous malformation (AVM)
- meningioma, glioma, primary CNS lymhoma
- spinal cord tumor
- cervical spondylosis herniated disc resulting in spinal cord compression
- transverse myelitis
- no CSF oligoclonal bands or CSF IgG index
- no lesions on brain MRI
- affects only one region of the spinal cord
- optic nerve involvement excludes the diagnosis
- medical disorders that cause transient neurologic dysfunction
- head trauma
* % of misdiagnoses from[69]
* migraine, microvascular ischemic disease & head trauma may also result in white matter MRI lesions[3]
Management
- symptomatic
- diagnosis with MRI prior to treatment
- fever exacerbates symptoms of multiple sclerosis (Uhthoff phenomenon)
- fatigue
- sleep hygiene, regular exercise, smoking cessation
- amantadine
- stimulants
- modafinil (Provigil)[3]
- armodafinil
- amphetamine[3]
- pemoline (Cylert)
- reserve for failure of response to amantadine & modafinil[5]
- not mentioned in MKSAP19[3]
- methylphenidate, modafinil, & amantadine no better than placebo[98]
- observe for depression
- depression is common[3]
- screen for depression
- counseling, suicide prevention
- antidepressants:
- SSRI or SNRI for patients with fatigue[5]
- TCA for patients with neuropathic pain[5]
- antipsychotics[3]
- cognitive impairment
- neuropsychologic testing
- cognitive rehabilitation, counseling, cognitive therapy[3][61]
- accomodation strategies
- no proven therapy
- spasticity
- treat if patient's ability to stand not dependent upon spasticity
- physical therapy, stretching, massage therapy
- medications for use in combination with physical therapy
- baclofen
- start 10 mg PO BID-TID; increase gradually
- severe, intractable spasticity generally responds to intrathecal baclofen (implantable pump)[3]
- tizanidine (alternative agent)[3]
- cyclobenzaprine, carisoprodol[3]
- benzodiazepine for nocturnal muscle spasm[5]
- Botox
- baclofen
- urinary urgency & incontinence
- scheduled toileting (bladder retraining) for urge incontinence
- anticholinergic agents for bladder spasticity (detrusor overactivity)
- oxybutynin, tolterodine, solefenacin[3]
- manual pelvic pressure & urinary catheterization for urinary retention
- post-void residual > 100 mL with anticholinergic therapy suggests significant urinary retention & the need for urologic evaluation
- urodynamic testing if mix of symptoms, uncertain etiology[3]
- constipation
- dietary fiber
- stool softener
- suppositories
- enemas
- lactulose
- neuralgic pain
- exercise, cognitive behavioral therapy, mind-body therapy
- physical therapy, acupuncture
- tricyclic antidepressant given QHS 1st line (low dose)[3][5]
- gabapentin (Neurontin): start 100 mg TID[5]
- carbamazepine (Tegretol): start 200 mg PO TID
- duloxetine[3]
- topiramate[3]
- capsaicin patch
- tramadol[3]
- chronic aching pain
- dysmetria
- isoniazid
- clonazepam
- tremor
- impaired mobility
- physical therapy, occupational therapy
- prosthetics: braces, cane, rollator, electrostimulatory walk devices[3]
- dalfampridine (Ampyra) may improve walking[3]
- pseudobulbar affect: dextromethorphan/quinidine
- exacerbations*
- distinguish relapse from pseudorelapse due to worsening of neurological symptoms due to another cause, i.e.infection other physiologic stressor[3]
- fever worsens symptoms of MS (pseudorelapse)[3]
- supportive therapy for pseudorelapse
- treat infection prior to administering methylprednisolone[3]
- methylprednisolone
- 1 g IV daily divided every 6 hours for 3-5 days for severe relapse[3]
- oral methylprednisolone & IV methylprednisolone equally effective for moderately severe relapse[50][54]
- methylprednisolone 1 g PO QD for 3 days[54]
- no such equivalence of oral prednisone[3]
- prednisone taper, avoid long-term glucocorticoid use
- glucocorticoids most effective for optic neuritis[3]
- ACTH IV or IM
- plasmapheresis for severe exacerbations not responding to corticosteroids[3]
- distinguish relapse from pseudorelapse due to worsening of neurological symptoms due to another cause, i.e.infection other physiologic stressor[3]
- relapsing/remitting progressive disease
- relapses with no or minimal effect on function may be observed & not treated[3]
- disease-modifying therapy can reduce rate of relapse, slow disability progression (including progression to secondary progressive MS), & reduce accumulation of new demyelinating lesions seen on MRI[3]
- self-injection with IFN-beta or glatiramer acetate 1st line[3]
- Avonex (interferon-beta 1a)
- betaseron (interferon-beta 1b)
- early treatment may diminish later disability[17]
- early treatment after acute demyelinating event delays 2nd event by 2.7 years[67]
- may not reduce progression of disability[33]
- vitamin D added to interferon-beta reduces demyelination on MRI[3]
- avoid interferon-beta in patients with liver disease or depression[3]
- glatiramer acetate (Copaxone) may delay progression of early MS[21]
- combining interferon-beta with glatiramer acetate no better than either agent alone[3]
- highly effective agents[99]
- natalizumab (Tysabri)[3][8][42] (increased risk of PML)
- alemtuzumab
- more effective than interferon-beta 1a, but with more severe adverse effects[34] (NICE)
- 40% lower rate of relapse vs IFN-beta but no effect on disability progression[72]
- lower annual relapse rate than fingolimod (0.15 vs 0.34) but no greater benefits on cumulative rate of relapse, disability worsening, & disability improvement[72]
- alemtuzumab & natalizumab with similar risks for relapse & disability worsening, but more patients appear to improve on natalizumab[72]
- ofatumumab (Arzerra, Kesimpta)
- ocrelizumab FDA-approved 2017[87]
- annual relapse rate higher in MS patients treated with rituximab vs ocrelizumab (0.20 vs 0.09)[107]
- mitoxantrone
- moderately effective agents[99]
- sphingosine-1-phosphate-receptor modulators
- fingolimod[3][22][44]
- risk of severe exacerbation of MS after stopping fingolimod[94]
- siponimod
- ponesimod (Ponvory)
- ozanimod
- dimethyl fumarate (NGC:NICE)
- off-label rituximab associated with fewer relapses over 2 years than dimethyl fumarate 3% vs 16%[106]
- cladribine
- sphingosine-1-phosphate-receptor modulators
- modestly effective agents
- teriflunomide
- glatiramer acetate
- interferon-beta 1a (AVonox)
- betaseron (interferon-beta 1b
- vitamin D added to interferon-beta reduces demyelination on MRI[3]
- combining interferon-beta with glatiramer acetate no better than either agent alone[3]
- others
- laquinimod (investigational)[31]
- copolymer-1 (COP-1) not mentioned in MKSAP17[3]
- calcitriol 2.5 ug/day (investigational)
- high-dose statin may be of benefit[48]
- primary progressive disease
- ocrelizumab only FDA-approved agent for primary progressive disease
- other agents not FDA-approved (2018)[3]
- cyclophosphamide
- methylprednisolone
- azathiaprine
- methotrexate 7.5 mg PO weekly
- bortezomib superior to dexamethasone for refractory MS[51]
- cladribine (investigational)
- Procarin (experimental)
- secondary progressive disease
- disease-modifying therapy of relapsing-remitting MS reduces conversion to secondary progressive disease[3]
- mitoxantrone, siponimod & cladribine only FDA-approved agents[3]
- potential benefit on disease progression[28]
- of limited use & potentially toxic
- discontinuation of disease-modifying therapy if non-ambulatory for > 2 years & have no relapsing activity during that time period[3]
- early possible multiple sclerosis (clinically isolated syndrome)*
- disease-modifying therapy reduces conversion to relapsing-remitting MS by ~50%[3]
- interferon-beta or glatiramer acetate[82]
- betaseron may be of benefit[6][7]
- avoid in patients with liver disease or depression[3]
- teriflunomide 7-14 mg PO QD reduces risk of recurrence* 37-42%[52]
- minocycline (investigational)[11]
- may prevent progression to multiple sclerosis in patients with an isolated demyelinating event (optic neuritis)[73]
- domperidone not useful[101]
- disease-modifying therapy
- cost effectiveness in question[29]
- should be started soon after diagnosis[86]
- reduces disease relapse & progression[3][86]
- of benefit for clinically isolated syndrome[3]
- discontinue if non-ambulatory for > 2 years without relapsing activity over same time period[3]
- stem cell transplantation
- investigational therapy for aggressive disease
- progression-free 15-year survival 25%[27]
- progression-free 5 year survival 46%[71]
- mortality 3% within 100 days of procedure[71]
- bortezomib in combination with dexamethasone +/- thalidomide for induction prior to high-dose chemotherapy with hematopoietic stem cell transplantation (NICE)
- bulsulfan vs total body irradiation (high-intensity) or cyclophosphamide +/- antithymocyte globulin or fludarabine phosphate for conditioning[71]
- treatment failure 6% vs 60% on drug therapy[85]
- alternative medicine therapy
- vitamin D +/- calcium may be of benefit[3][57]
- cannabis extract, tetrahydrocannabinol, or cannabinoid spray may ease patient- reported spasticity & pain (excluding central neuropathic pain)[49]
- likely not effective in improving objective measures of spasticity[49]
- MKSAP19 suggests cannabis useful for treating refractory spasticity & pain[3]
- may help reduce urinary frequency[49]
- cannabinoids with small if any benefit[93]
- high-dose biotin ineffective[97]
- cognitive impairment
- neuropsychologic testing, counseling, cognitive therapy[3][61]
- accomodation strategies
- no proven therapy
- exercise & physical therapy
- regular exercise may minimize disability[3]
- stretching exercises can help reduce spasticity, & prevent painful muscle cramps[3]
- supervised sessions in a vestibular rehabilitation program, with daily home exercises, improve balance, quality of life, & fatigue[83]
- diet plays a role
- high fat intake is associated with increased risk for multiple sclerosis relapse in children
- association appears to be with saturated fat
- high vegetable intake might be protective[76]
- a Mediterranean diet is associated with better cognition[110]
- health maintenance
- immunizations recommended to minimize risk of infection
- infections increase risk of relapse[3][46]
- annual influenza vaccination recommended[3]
- immunizations should be delayed for 4-6 weeks after an acute attack
- live virus vaccines should not be administered to patientson immunosuppressive therapy[3]
- immunizations recommended to minimize risk of infection
- patient education
- treatments are expensive, hazardous
- acute infections can trigger MS exacerbations
- no therapies have proven benefits on the neurodegeneration that occurs with progressive multiple sclerosis[3]
- venoplasty has no role in treatment of MS[37]
- smoking cessation:
- National Multiple Sclerosis Foundation provides supplementary patient information
- pregnancy & lactation
- hormonal state of pregnancy itself is protective against disease activity[3]
- women with MS experience an increased risk of relapse after delivery[55]
- pregnancy does not cause additional permanent disability in women with MS[3]
- exclusive breastfeeding may reduce postpartum risk of MS relapse[55]
- return of menstruation may mitigate the reduced risk of relapse
- childbirth may have favorable long-term effect on course of multiple sclerosis[63]
- have > 1 child & breast feeding > 15 months reduces risk for multiple sclerosis in mothers[74]
* exacerbations with be precipitated by infection (3-fold risk) or stress (2-fold risk)[10]
* clinically isolated syndrome = first clinical episode suggestive of multiple sclerosis[52]
- Follow-up:
- regular reassessment of patient's condition
- interferon beta-1b may cause leukopenia & elevation of serum transaminases: follow-up once a month for 3 months, then once every 3 months
- watch for symptoms of depression
- Prognosis:
- Prevention:
- supplemental vitamin D 1000-2000 IU daily to high-risk pregnant women & breast-feeding mothers with low serum 25-OH vitamin D levels (<20 ng/mL) & an immediate family member with MS[70]
- a diet rich in fish & omega-3 polyunsaturated fatty acids may diminish risk of multiple sclerosis[84]
- 1/2 hour of sunlight/day may cut risk of MS in 1/2[103]
- treatment of obesity or type-2 diabetes lowers risk of MS[116]
- semaglutide lowers risk of MS by 76%
- dulaglutide lowers risk of MS by 84%
- liraglutide lowers risk of MS by 84%
- empagliflozin lowers risk of MS by 77%
- metformin lowers risk of MS by 61%[116]
Comparative biology
- miconazole & clobetasol promote remyelination in mouse demyelinating disease
- these 2 agents induced mouse oligodendrocyte-progenitor stem cells to turn into myelin-producing oligodendrocytes[53]
More general terms
More specific terms
- multiple sclerosis variants
- Schilder's disease; myelinoclastic diffuse sclerosis; balo concentric sclerosis
Additional terms
- experimental autoimmune encephalomyelitis
- neuropsychologic testing
- oligoclonal banding in CSF (high-resolution CSF protein electrophoresis)
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1058-60
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 723
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 3.30 3.31 3.32 3.33 3.34 3.35 3.36 3.37 3.38 3.39 3.40 3.41 3.42 3.43 3.44 3.45 3.46 3.47 3.48 3.49 3.50 3.51 3.52 3.53 3.54 3.55 3.56 3.57 3.58 3.59 3.60 3.61 3.62 3.63 3.64 3.65 3.66 3.67 3.68 3.69 3.70 3.71 3.72 3.73 3.74 3.75 3.76 3.77 3.78 3.79 3.80 3.81 3.82 3.83 3.84 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ The Prescriber's Letter, vol 6 #11, Nov 1999
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Prescriber's Letter 8(6):35 2001
- ↑ 6.0 6.1 Journal Watch 21(13):103, 2001 Comi G et al Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576, 2001 Ebers Lancet 357:15747, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11377645
- ↑ 7.0 7.1 Journal Watch 20(11):169, 2000 McDonald WI. Relapse, remission, and progression in multiple sclerosis. N Engl J Med. 2000 Nov 16;343(20):1486-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11078776
Confavreux C et al Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000 Nov 16;343(20):1430-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11078767 [PubMed - indexed for MEDLINE]
Noseworthy JH et al Multiple sclerosis N Engl J Med. 2000 Sep 28;343(13):938-52. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11006371 - ↑ 8.0 8.1 Journal Watch 23(4):34, 2003 Miller DH et al, A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12510038
von Andrian UH & Engelhardt B Alpha4 integrins as therapeutic targets in autoimmune disease. N Engl J Med 348:68, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12510047 - ↑ 9.0 9.1 van der Mei IA et al Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ. 2003 Aug 9;327(7410):316. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12907484
- ↑ 10.0 10.1 Journal Watch 23(22):179, 2003 Buljevac D et al, BMJ 327:646, 2003 http://bmj.com/cgi/content/full/327/7416/646 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14500435
- ↑ 11.0 11.1 NIH workshop on "Glial inflammation" Dec 2003
- ↑ 12.0 12.1 Leven LI et al. Temporal Relationship Between Elevation of Epstein-Barr Virus Antibody Titers and Initial Onset of Neurological Symptoms in Multiple Sclerosis, JAMA 293:2496-2500, 2005 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15914750
- ↑ 13.0 13.1 VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr. 2004 Aug;58(8):1095-109. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15054436
Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14718698 - ↑ Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1294-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16107372
- ↑ Munger KL et al, Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006, 296:2832 http://jama.ama-assn.org/cgi/content/full/296/23/2832
- ↑ Correale J et al, The risk of relapses in multiple sclerosis during systemic infections. Neurology 2006, 67:652 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16870812
- ↑ 17.0 17.1 Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Radu EW, Bauer L, Dahms S, Lanius V, Pohl C, Sandbrink R; BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007 Aug 4;370(9585):389-97. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17679016
Pittock SJ. Interferon beta in multiple sclerosis: how much BENEFIT? Lancet. 2007 Aug 4;370(9585):363-4. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17678997 - ↑ Ousman SS et al, Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature 2007, 448:474 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17568699
Ransohoff RM Inflammatory disease: Assault on the guardian. Nature 2007, 448:421 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17653181 - ↑ Gregory SG et al, Interleukin 7 receptr alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 2007, 30:1083 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17660817
Lundmark F et al, Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet 2007, 39:1108 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17660816 - ↑ Burt RK et al Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study The Lancet Neurology, 30 January 2009 doi:10.1016/S1474-4422(09)70017-1
- ↑ 21.0 21.1 Comi G et al, Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double- blind, placebo-controlled trial The Lancet, Early Online Publication, 7 October 2009 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19815268 doi:10.1016/S0140-6736(09)61259-9 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961259-9/abstract
- ↑ 22.0 22.1 Kappos L et al A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis NEJM www.nejm.org January 20, 2010 http://content.nejm.org/cgi/content/full/NEJMoa0909494
Cohen JA et al Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis NEJM www.nejm.org January 20, 2010 http://content.nejm.org/cgi/content/full/NEJMoa0907839 - ↑ 23.0 23.1 Baranzini SE et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 2010 Apr 29; 464:1351. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20428171
- ↑ Walter U et al. Transcranial brain sonography findings predict disease progression in multiple sclerosis. Neurology 2009 Sep 29; 73:1010. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19657105
- ↑ 25.0 25.1 25.2 Polman CH et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the "McDonald criteria." Ann Neurol 2011 Jan 11; PMID: https://www.ncbi.nlm.nih.gov/pubmed/21387374
- ↑ 26.0 26.1 26.2 Lucas RM et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011 Feb 8; 76:540. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21300969 <Internet> http://www.neurology.org/content/76/6/540.full http://dx.doi.org/10.1002/ana.22366
- ↑ 27.0 27.1 Fassas A et al. Long-term results of stem cell transplantation for MS: A single-center experience. Neurology 2011 Mar 22; 76:1066. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21422458 <Internet> http://www.neurology.org/content/76/12/1066.full
- ↑ 28.0 28.1 Marriott JJ et al Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010 May 4;74(18):1463-70 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20439849
- ↑ 29.0 29.1 Noyes K et al Cost-effectiveness of disease-modifying therapy for multiple sclerosis: A population-based study Neurology 2011, 77(3) July 20, <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21775734 <Internet> http://www.neurology.org/content/early/2011/07/20/WNL.0b013e3182270402.abstract
- ↑ Berer K et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011 Nov 24; 479:538 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22031325
- ↑ 31.0 31.1 Journal Watch, Massachusetts Medical Society, March 15, 2012 Comi G et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 2012 Mar 15; 366:1000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22417253
- ↑ 32.0 32.1 ARUP Consult: Multiple Sclerosis The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/multiple-sclerosis
- ↑ 33.0 33.1 Shirani A et al Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis JAMA. 2012;308(3):247-256 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22797642 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1217239
Derfuss T and Kappos L Evaluating the Potential Benefit of Interferon Treatment in Multiple Sclerosis JAMA. 2012;308(3):290-291 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22797647 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1217217 - ↑ 34.0 34.1 Cohen JA et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: A randomised controlled phase 3 trial. Lancet 2012 Nov 24; 380:1819. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23122652
Coles AJ et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet 2012 Nov 24; 380:1829. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23122650 - ↑ 35.0 35.1 Sombekke MH et al. Spinal cord lesions in patients with clinically isolated syndrome: A powerful tool in diagnosis and prognosis. Neurology 2013 Jan 1; 80:69 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23243070
- ↑ Prescriber's Letter 20(5): 2013 Chart: Drug Treatments for Multiple Sclerosis Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=290512&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 37.0 37.1 37.2 Traboulsee AL et al Prevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case-control study. The Lancet, Early Online Publication, 9 October 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24119384 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61747-X/abstract
Paul F and Wattjes MP Chronic cerebrospinal venous insufficiency in multiple sclerosis: the final curtain. The Lancet, Early Online Publication, 9 October 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24119383 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61912-1/fulltext - ↑ Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010 Aug;33(8):1061-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20815187
- ↑ Goodin DS, Frohman EM, Garmany GP Jr et al Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002 Jan 22;58(2):169-78. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11805241
- ↑ Frohman EM, Goodin DS, Calabresi PA et al The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003 Sep 9;61(5):602-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12963748
- ↑ Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. 2006 Mar 2;354(9):942-55. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16510748
- ↑ 42.0 42.1 Goodin DS, Cohen BA, O'Connor P et al Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008 Sep 2;71(10):766-73 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18765653
- ↑ Hiremath GS, Cettomai D, Baynes M Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Mult Scler. 2009 Jun;15(6):735-40 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19383644
- ↑ 44.0 44.1 Kappos L, Radue EW, O'Connor P et al A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):387-401 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20089952
- ↑ 45.0 45.1 Polman CH, Reingold SC, Edan G et al Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16283615
- ↑ 46.0 46.1 Rutschmann OT, McCrory DC, Matchar DB et al Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002 Dec 24;59(12):1837-43. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12499473
- ↑ 47.0 47.1 Ascherio A et al Vitamin D as an Early Predictor of Multiple Sclerosis Activity and Progression. JAMA Neurol. Published online January 20, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24445558 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1815002
- ↑ 48.0 48.1 Chataway J et al Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. The Lancet, Early Online Publication, 19 March 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24655729 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962242-4/abstract
Palace J and Robertson N Modifying disability in progressive multiple sclerosis The Lancet, Early Online Publication, 19 March 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24655728 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962641-0/fulltext - ↑ 49.0 49.1 49.2 49.3 Yadav V et al Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis. Neurology March 25, 2014 vol. 82 no. 12 1083-1092 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24663230 <Internet> http://www.neurology.org/content/82/12/1083.full
- ↑ 50.0 50.1 Ramo-Tello C et al. A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS. Mult Scler 2014 May; 20:717. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24144876 <Internet> http://msj.sagepub.com/content/20/6/717
- ↑ 51.0 51.1 Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15958804
- ↑ 52.0 52.1 52.2 Miller AE et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014 Oct; 13:977. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25192851 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2814%2970191-7/fulltext
- ↑ 53.0 53.1 Najm FJ et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 2015 Jun 11; 522:216. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25896324
- ↑ 54.0 54.1 54.2 Le Page E et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): A randomised, controlled, double-blind, non- inferiority trial. Lancet 2015 Jun 26; PMID: https://www.ncbi.nlm.nih.gov/pubmed/26135706
- ↑ 55.0 55.1 55.2 Hellwig K et al. Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses. JAMA Neurol 2015 Aug 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26322399
- ↑ Murray SG et al A Breakthrough Diagnosis N Engl J Med 2015; 373:1865-1870. November 5, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26535516 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcps1402621
- ↑ 57.0 57.1 Golan D, Halhal B, Glass-Marmor L et al Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties. BMC Neurol. 2013 Jun 14;13:6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23767916
- ↑ de Sa JC, Airas L, Bartholome E et al Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice. Ther Adv Neurol Disord. 2011 May;4(3):139-68 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21694816
- ↑ Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2012 Dec 12;12:CD006921 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23235634
- ↑ 60.0 60.1 Mowry EM, Waubant E, McCulloch CE et al Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol. 2012 Aug;72(2):234-40. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22926855
- ↑ 61.0 61.1 61.2 Benedict RH1, Zivadinov R Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol. 2011 May 10;7(6):332-42 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21556031
- ↑ Rubin SM. Management of multiple sclerosis: an overview. Dis Mon. 2013 Jul;59(7):253-60 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23786659
- ↑ 63.0 63.1 D'hooghe MB, Nagels G, Uitdehaag BM. Long-term effects of childbirth in MS. J Neurol Neurosurg Psychiatry. 2010 Jan;81(1):38-41 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19939856
- ↑ Thrower BW Relapse management in multiple sclerosis. Neurologist. 2009 Jan;15(1):1-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19131851
- ↑ Amato MP, Portaccio E. Management options in multiple sclerosis-associated fatigue. Expert Opin Pharmacother. 2012 Feb;13(2):207-16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22220738
- ↑ 66.0 66.1 Munger KL, Aivo J, Hongell K et al Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort. JAMA Neurol. Published online March 07, 2016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26953778 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2499458
- ↑ 67.0 67.1 Kappos L, Edan G, Freedman MS et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology 2016 Aug 10; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27511182
- ↑ 68.0 68.1 68.2 Dorans KS et al. Physical activity and the incidence of multiple sclerosis. Neurology 2016 Sept 28; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27683852 <Internet> http://www.neurology.org/content/early/2016/09/28/WNL.0000000000003260
- ↑ 69.0 69.1 69.2 69.3 Wilner AN Diagnostic Error in Patients With Neurologic Symptoms. Medscape. Oct 31, 2016 http://www.medscape.com/features/slideshow/diagnostic-errors/neurologic
- ↑ 70.0 70.1 70.2 Nielsen NM, Munger KL, Koch-Henriksen N et al Neonatal vitamin D status and risk of multiple sclerosis. A population-based case-control study. Neurology. Nov 30, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27903815 <Internet> http://www.neurology.org/content/early/2016/11/30/WNL.0000000000003454
Marrie RA, Daumer M. A gestational dose of vitamin D per day keeps the MS doctor away. Neurology. Nov 30, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27903816 <Internet> http://www.neurology.org/content/early/2016/11/30/WNL.0000000000003469 - ↑ 71.0 71.1 71.2 71.3 Muraro PA, Pasquini M, Atkins HL et al Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol. Published online February 20, 2017 http://jamanetwork.com/journals/jamaneurology/fullarticle/2604135
- ↑ 72.0 72.1 72.2 72.3 Kalincik T, Brown JW, Robertson N et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: A cohort study. Lancet Neurol 2017 Apr; 16:271 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28209331 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30007-8/abstract
- ↑ 73.0 73.1 Metz LM, Li DK, Traboulsee AL et al Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. N Engl J Med 2017; 376:2122-2133. June 1, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28564557 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1608889
- ↑ 74.0 74.1 Langer-Gould A, Smith JB, Hellwig K et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurol (Tokyo) 2017 Jul 12; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28701499 <Internet> http://www.neurology.org/content/early/2017/07/07/WNL.0000000000004207
- ↑ 75.0 75.1 Munger KL, Hongell K, Aivo J et al 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. Sept 13, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28904091 <Internet> http://www.neurology.org/content/early/2017/09/13/WNL.0000000000004489
Marrie RA, Beck CA Preventing multiple sclerosis. To (take) vitamin D or not to (take) vitamin D? Neurology. Sept 13, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28904085 <Internet> http://www.neurology.org/content/early/2017/09/13/WNL.0000000000004506 - ↑ 76.0 76.1 Azary S, Schreiner T, Graves J et al Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry 2017. Oct 9 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28993476 <Internet> http://jnnp.bmj.com/content/early/2017/09/01/jnnp-2017-315936
Fitzgerald K Diet and disease modification in multiple sclerosis: a nutritional epidemiology perspective. Journal of Neurology, Neurosurgery & Psychiatry 2017. Oct 9 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28993475 <Internet> http://jnnp.bmj.com/content/early/2017/09/01/jnnp-2017-316375 - ↑ 77.0 77.1 Fiore K. Protein May Be Marker of MS Disease Severity, Remyelination - Early work suggests beneficial effect of IL4I1 in multiple sclerosis. MedPage Today. Nov 13, 2017 https://www.medpagetoday.com/meetingcoverage/sfn/69252
Davis S, et al Interleukin-4 induced protein 1 as a biomarker and treatment option in multiple sclerosis. Society for Neuroscience (SfN) 2017; Abstract 304.08/X30 - ↑ 78.0 78.1 Fiore K. Methionine Metabolism Disrupted in MS - Particularly impacted in progressive disease. MedPage Today. Nov 14, 2017 https://www.medpagetoday.com/meetingcoverage/sfn/69274
Mir F, et al Methionine metabolism is altered in multiple sclerosis. Society for Neuroscience (SfN) 2017; Abstract 475.16/N2. - ↑ 79.0 79.1 Jenkins K Serum Biomarker May Predict Relapse in MS High NF-L levels could identify subclinical disease activity. MedPage Today. Nov 30, 2017
Varhaug KN, Barro C, Bjornevik K et al Neurofilament light chain predicts disease activity in relapsing-remitting MS Neurol. Published Online Nov 29, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29209636 <Internet> http://nn.neurology.org/content/5/1/e422 - ↑ Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med 2018; 378:169-180. January 11, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29320652 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMra1401483
- ↑ 81.0 81.1 Thompson AJ, Banwell BL, Barkhof F et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2017 Dec 21; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29275977 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30470-2/fulltext
Bove RM, Hauser SL. Diagnosing multiple sclerosis: Art and science. Lancet Neurol 2017 Dec 21 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29275980 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30461-1/fulltext - ↑ 82.0 82.1 Hughes S European MS Treatment Guidelines Released Medscape - Oct 27, 2017. https://www.medscape.com/viewarticle/887730
- ↑ 83.0 83.1 Hebert JR, Corboy JR, Vollmer T, Forster JE, Schenkman M. Efficacy of Balance and Eye-Movement Exercises for Persons with Multiple Sclerosis (BEEMS). Neurology 2018 Jan 31; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29386274 <Internet> http://n.neurology.org/content/early/2018/01/31/WNL.0000000000005013
- ↑ 84.0 84.1 George J Omega-3s Linked to Lower MS Risk. Fatty acid biosynthesis may play a protective role. MedPage Today. March 01, 2018 https://www.medpagetoday.com/meetingcoverage/aan/71464
Langer-Gould A, et al Fish, fatty acid biosynthesis genes, and multiple sclerosis susceptibility. American Academy of Neurology (AAN) 2018. - ↑ 85.0 85.1 Sheffield Teaching Hospitals news release. March 19, 2018 MS stem cell treatment stabilises disease and reduces disability, trial shows. http://www.sth.nhs.uk/news/news?action=view&newsID=1035
Walsh F Stem cell transplant 'game changer' for MS patients BBC News. March 18, 2018 http://www.bbc.com/news/health-43435868 - ↑ 86.0 86.1 86.2 Rae-Grant A, Day GS, Marrie RA et al Practice guideline recommendations summary: Disease- modifying therapies for adults with multiple sclerosis Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Apr 24;90(17):777-788 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29686116 <Internet> http://n.neurology.org/content/90/17/777
Rae-Grant A, Day GS, Marrie RA et al Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Apr 24;90(17):789-800 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29686117 <Internet> http://n.neurology.org/content/90/17/789
Chitnis T, Giovannoni G, Trojano M. Complexity of MS management in the current treatment era. Neurology. April 24, 2018; 90 (17) <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29686111 <Internet> http://n.neurology.org/content/90/17/761 - ↑ 87.0 87.1 Boyles S MRI Improvements in MS with Switch from IFN to Ocrelizumab. Rapid and robust reduction in activity. MedPage Today. June 4, 2018 https://www.medpagetoday.com/meetingcoverage/cmsc/73267
Troboulsee A, et al Brain MRI activity and atrophy in ocrelizumab-treated relapsing multiple sclerosis patients in the open-label extension of the pooled OPERA trials. Consortium of Multiple Sclerosis Centers (CMSC) 2018; Abstract #DX45. - ↑ 88.0 88.1 Hedstrom AK et al. Organic solvents and MS susceptibility: Interaction with MS risk HLA genes. Neurology 2018 Jul 31; 91:e455. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29970406
Bell JS, DeLuca GC. Genes, smoking, and organic solvent exposure: An alarming cocktail for MS risk. Neurology 2018 Jul 31; 91:199 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29970400 - ↑ Phe V, Chartier-Kastler E, Panicker JN. Management of neurogenic bladder in patients with multiple sclerosis. Nat Rev Urol. 2016 May;13(5):275-88. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27030526
- ↑ Wingerchuk DM, Weinshenker BG. Disease modifying therapies for relapsing multiple sclerosis. BMJ. 2016 Aug 22;354:i3518. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27549763
- ↑ Soilu-Hsnninen M, Aivo J, Lindstrom BM et al A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 May;83(5):565-71. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22362918
- ↑ Lublin FD, Reingold SC, Cohen JA et a; Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24871874 Free PMC Article
- ↑ 93.0 93.1 Torres-Moreno MC, Papaseit E,Torrens M, et al Assessment of Efficacy and Tolerability of Medicinal Cannabinoids in Patients With Multiple SclerosisA Systematic Review and Meta-analysis. JAMA Network Open. 2018;1(6):e183485. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30646241 Free PMC Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706499
Slaven M, Levine O. Cannabinoids for Symptoms of Multiple Sclerosis. Benefits to Patients Still Unclear. JAMA Network Open. 2018;1(6):e183484 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2706491 - ↑ 94.0 94.1 FDA Safety Alert. Nov 20, 2018 Gilenya (fingolimod): Drug Safety Communication - Severe Worsening of Multiple Sclerosis After Stopping the Medicine. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm626264.htm
- ↑ Farez MF, Corrleale J, Armstrong MJ et al Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. Aug 28, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31462584 https://n.neurology.org/content/early/2019/08/28/WNL.0000000000008157
- ↑ 96.0 96.1 Singhal T et al. Regional microglial activation in the substantia nigra is linked with fatigue in MS. Neurol Neuroimmunol Neuroinflamm 2020 Sep; 7:e854. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32769103 Free article. https://nn.neurology.org/content/7/5/e854
- ↑ 97.0 97.1 Nackerdien Z End of the Road for High-Dose Biotin in Progressive MS? MedPage Today 2020-11-08 https://www.medpagetoday.org/neurology/multiplesclerosis/89542
Cree BAC, Cutter G, Wolinsky JS et al Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurology. 2020. Oct 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33222767 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30347-1/fulltext
Motte J, Gold R High-dose biotin in multiple sclerosis: the end of the road. Lancet Neurology. 2020. Oct 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33222766 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30353-7/fulltext - ↑ 98.0 98.1 Nourbakhsh B, Revirajan N, Morris B et al Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol 2020, Nov 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33242419 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30354-9/fulltext
- ↑ 99.0 99.1 99.2 Hauser SL, Cree BAC Treatment of Multiple Sclerosis: A Review. American Journal of Medicine 2020. 133:1380=1390. Dec PMID: https://www.ncbi.nlm.nih.gov/pubmed/32682869 PMCID: PMC7704606 https://www.amjmed.com/article/S0002-9343(20)30602-1/fulltext
- ↑ 100.0 100.1 100.2 Midaglia L, Sastre-Garriga J, Pappolla A et al. The frequency and characteristics of MS misdiagnosis in patients referred to the multiple sclerosis centre of Catalonia. Mult Scler 2021 Feb 10; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33565909 https://journals.sagepub.com/doi/10.1177/1352458520988148
- ↑ 101.0 101.1 George J Repurposed Drug Flops in MS Trial, but Study Design Is Big Winner. Simon two-stage futility study seen as model for mid-stage trials MedPage Today March 26, 2021 https://www.medpagetoday.com/neurology/multiplesclerosis/91836
Koch MW, Sage K, Kaur S et al Repurposing domperidone in secondary progressive MS: a Simon 2-stage phase 2 futility trial. Neurology 2021. March 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34038379 https://n.neurology.org/content/early/2021/03/23/WNL.0000000000011863
Fox RJ, Kryscio RJ A new way to identify promising therapies for progressive MS. Neurology 2021. March 23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34038382 https://n.neurology.org/content/early/2021/03/23/WNL.0000000000011862 - ↑ 102.0 102.1 George J Quitting Smoking Tied to Slower Motor Decline in Multiple Sclerosis Analysis suggests smoking cessation has benefits in MS. MedPage Today October 17, 2021 https://www.medpagetoday.com/meetingcoverage/ectrims/95089
- ↑ 103.0 103.1 Swift Yasgur B Half an Hour of Daily Sun Exposure Cuts MS Risk in Half. Medscape. December 14, 2021 https://www.medscape.com/viewarticle/964775
Sebastian P, Cherbuin N, Barcellos LF et al Association Between Time Spent Outdoors and Risk of Multiple Sclerosis. Neurology. 2021. December 8. https://n.neurology.org/content/early/2021/12/07/WNL.0000000000013045.long - ↑ 104.0 104.1 George J MS Risk Skyrockets After Epstein-Barr Virus, but Not Other Infections. Findings show "compelling evidence of causality". MedPage Today January 13, 2022 https://www.medpagetoday.com/neurology/multiplesclerosis/96656
Bjornevik K, Cortese M, Healy BC et al Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022. Jan 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35025605 https://www.science.org/doi/10.1126/science.abj8222 - ↑ 105.0 105.1 105.2 Vitkova M, Diouf T, Malpas C et al Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study. Neurology. 2022. April 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35410900 https://n.neurology.org/content/early/2022/04/11/WNL.0000000000200545
- ↑ 106.0 106.1 Jenks S Off-Label Drug Lowers Relapses in Multiple Sclerosis. Study paves way for rituximab to be considered for MS in some countries. MedPage Today. July 21, 2022 https://www.medpagetoday.com/neurology/multiplesclerosis/99838
Svenningsson A et al Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial. Lancet Neurology. 2022. August PMID: https://www.ncbi.nlm.nih.gov/pubmed/35841908 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00209-5/fulltext - ↑ 107.0 107.1 George J Higher Relapse Rate With Rituximab vs Ocrelizumab in MS Registry Data. Rituximab did not show non-inferiority in comparative effectiveness study. MedPage Today November 1, 2022 https://www.medpagetoday.com/meetingcoverage/ectrims/101534
- ↑ 108.0 108.1 Meier S, Willemse EAJ, Schaedelin S et al Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis. JAMA Neurol. Published online February 6, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36745446 https://jamanetwork.com/journals/jamaneurology/fullarticle/2801290
- ↑ 109.0 109.1 109.2 Varelas AN, Dickstein L, Eytan DF. Episodic Facial Paresis-An Isolated Presenting Symptom of Multiple Sclerosis JAMA Otolaryngol Head Neck Surg. 2023 Feb 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36757719
JN Learning. Video Brain Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI). JAMA Otolaryngol Head Neck Surg. 2023. Feb 9 https://edhub.ama-assn.org/jn-learning/video-player/18756537 - ↑ 110.0 110.1 George J Cognitive Impairment in Multiple Sclerosis Tied to Diet. Mediterranean diet was strongest predictor of better cognitive scores. MedPage Today March 3, 2023 https://www.medpagetoday.com/meetingcoverage/aan/103374
- ↑ 111.0 111.1 111.2 111.3 111.4 111.5 Solomon AJ et al. Differential diagnosis of suspected multiple sclerosis: An updated consensus approach. Lancet Neurol 2023 Aug; 22:750. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37479377 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00148-5/fulltext
- ↑ NINDS Multiple Sclerosis Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Multiple-Sclerosis-Information-Page
- ↑ Olek MJ. Multiple sclerosis. Ann Intern Med. 2021;174:ITC81-ITC96. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34097429
- ↑ 114.0 114.1 114.2 He A, Manouchehrinia A, Glaser A et al Premorbid Sociodemographic Status and Multiple Sclerosis Outcomes in a Universal Health Care Context. JAMA Netw Open. 2023;6(9):e2334675. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37751208 PMCID: PMC10523174 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809932
- ↑ 115.0 115.1 Mouresan EF et al. Clinical characteristics and long-term outcomes of late-onset multiple sclerosis: A Swedish nationwide study. Neurology 2024 Mar 26; 102:e208051. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38394472 https://www.neurology.org/doi/10.1212/WNL.0000000000208051
- ↑ 116.0 116.1 116.2 Shirani A, Cross AH, Stuve O Exploring the association between weight loss-inducing medications and multiple sclerosis: insights from the FDA adverse event reporting system database. Ther Adv Neurol Disord. 2024 Apr 1;17:17562864241241383 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38566910 PMCID: PMC10986166 Free PMC article https://journals.sagepub.com/doi/10.1177/17562864241241383
- ↑ 117.0 117.1 Giordano A, Clarelli F, Pignolet B et al Vitamin D affects the risk of disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2024 Jul 14:jnnp-2024-334062. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39004505 https://jnnp.bmj.com/content/early/2024/07/13/jnnp-2024-334062
- ↑ 118.0 118.1 Brier MR, Schindler SE, Salter A et al Unexpected Low Rate of Amyloid-beta Pathology in Multiple Sclerosis Patients. Ann Neurol. 2024 Sep;96(3):453-459 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38963256 PMCID: PMC11324391 (available on 2025-09-01)
- ↑ 119.0 119.1 George J Blood Markers Help Predict MS Disease Progression. Patients with high NfL at disease onset may benefit from high-efficacy treatments. MedPage Today September 19, 2024 https://www.medpagetoday.com/meetingcoverage/ectrims/112039
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