Guideline sources The following summarized guidelines for the evaluation and management of multiple sclerosis (MS) are prepared by our editorial team based on guidelines from the Canadian Expert Group on Cannabinoids Use in Chronic Pain (CCP-CEG 2023), the Infectious Diseases Society of America (IDSA/ACR/AAN 2021), the American Academy of Sleep Medicine (AASM 2021), the European Society for Neurogastroenterology and Motility (ESNM/UEG 2021), the American College of Radiology (ACR 2021), the European Academy of Neurology (EAN 2020), the Middle East North Africa Committee for Research and Treatment in Multiple Sclerosis (MENACTRIMS 2020), the Latin American Consensus Group on Neuromyelitis Optica Spectrum Disorder (LACG-NMOSD 2020), the American Academy of Neurology (AAN 2019; 2018; 2016; 2014; 2002), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/EAN 2018), the American College of Gastroenterology (ACG 2018), and the European Federation of Neurological Societies (EFNS 2010; 2005). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 19 20 21 22 23 23 Definition MS is a chronic immune-mediated disease, characterized by demyelinating lesions in the brain and spinal cord. 19 https://web.pathway.md/diseases/recUn6IGFcair5i4r 1/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Epidemiology Demyelinating lesions are thought to result from migration of autoreactive lymphocytes across the blood-brain barrier, which triggers a cascade of inflammation with T- and B-cell clonal expansion and activation of microglia, leading to the development of characteristic plaque Genetic factors (HLA-DRB1 haplotype) and environmental factors (viruses, low vitamin D, distance from the equator) have been implicated. 21 22 Pathophysiology The prevalence of MS varies markedly geographically. In the United States, MS has an estimated prevalence of 149.2 persons per 100,000 population. Incidence has been estimated at 17.3 cases per 100,000 person-years in Western Europe. 19 20 Disease course The clinical manifestations of MS are wide ranging. Common presenting features include weakness, paresthesia or focal sensory loss, optic neuritis, diplopia, ataxia and vertigo. Autonomic dysfunction is common, and may manifest as bladder, bowel and sexual symptoms. Other manifestations can include painful muscle spasms, trigeminal neuralgia, fatigue and depression, subtle cognitive difficulties, psychiatric disturbances and seizures. 23 Prognosis and risk of recurrence MS typically follows a relapsing and remitting course, but it can be progressive from disease onset, or can become progressive after initial remissions. The interval between relapses is variable. The latent phase between the first manifestation of MS and the first relapse can be many years. 23 Guidelines 1. Screening and diagnosis Differential diagnosis (neuromyelitis optica): rule out MS in patients with suspected neuromyelitis optica spectrum disorder. E Differential diagnosis (Lyme disease): do not test for Lyme disease routinely in patients with typical relapsing-remitting MS. D Associated comorbidities (Crohn's disease): recognize that MS can be associated with Crohn's disease. E Associated comorbidities (gastroparesis): recognize that MS is associated with an increased risk for the development of gastroparesis. B 2. Diagnostic investigations https://web.pathway.md/diseases/recUn6IGFcair5i4r 2/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Diagnostic imaging: obtain spinal cord MRI as initial imaging in patients with acute onset or chronic/progressive myelopathy. B 3. Medical management Management of clinically isolated syndrome: As per MENACTRIMS 2020 guidelines, obtain close follow-up for the development of a clinical event in patients with radiologically isolated syndrome. Do not initiate disease-modifying therapies in patients with radiologically isolated syndrome. E As per AAN 2018 guidelines: Consider obtaining close follow-up with serial imaging rather than initiating DMT in patients with clinically isolated syndrome. C Review the associated risks of continuing versus stopping disease-modifying therapies, when initiated, in patients with clinically isolated syndrome. B As per EAN 2018 guidelines: Initiate early DMT in patients with clinically isolated syndrome fulfilling current diagnostic criteria for MS. A Initiate interferon or glatiramer acetate in patients with clinically isolated syndrome and abnormal MRI with lesions suggestive of MS not fulfilling criteria for MS. A Management of acute relapses, corticosteroids: As per MENACTRIMS 2020 guidelines, administer IV methylprednisolone 500-1,000 mg/day for 3-5 days for the treatment of acute MS relapses. E As per EFNS 2005 guidelines, consider administering IV or PO methylprednisolone at least 500 mg/day for 5 days for the treatment of relapses. B Consider administering IV methylprednisolone 1 g once daily for 3 days as an alternative treatment. E Show 3 more As per AAN 2002 guidelines: Consider administering short-term corticosteroids in patients with an acute attack of MS. B Consider administering regular pulse corticosteroids for the long-term management of patients with relapsing-remitting MS. C Management of acute relapses, plasma exchange: As per MENACTRIMS 2020 guidelines, consider performing plasma exchange for the treatment of patients with severe disabilities not responding to IV corticosteroids. E As per AAN 2002 guidelines: Avoid performing plasma exchange for the treatment of progressive MS. D Consider performing plasma exchange for severe acute episodes of demyelination in previously non-disabled patients. C Management of acute relapses (IVIG): insufficient evidence to recommend IVIG monotherapy for the management of relapses. Do not use IVIG as an add-on to methylprednisolone in patients https://web.pathway.md/diseases/recUn6IGFcair5i4r 3/13 6/30/23, 1:06 AM Multiple sclerosis Pathway with relapses or as monotherapy for acute optic neuritis. I Disease-modifying therapies, indications: As per AAN 2018 guidelines, initiate disease-modifying therapies in patients with relapsing forms of MS with recent clinical relapses or MRI activity. B Show 2 more As per EAN/ECTRIMS 2018 guidelines: Initiate early DMT in patients with active relapsing-remitting MS, as defined by clinical relapses and/or MRI activity (active lesions-contrast-enhancing lesions, new or unequivocally enlarging T2 lesions assessed at least annually). A Prescribe disease-modifying drugs only in centers with adequate infrastructure to provide proper monitoring, comprehensive assessment, and detection of side effects and capacity to address them promptly. E Disease-modifying therapies (pretreatment counseling): Counsel patients with MS on the following topics: specific treatment options with disease-modifying therapies (at a dedicated treatment visit) disease-modifying therapies are prescribed to reduce relapses and new MRI lesion activity but not for symptom improvement risk of progressive multifocal leukoencephalopathy associated with natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about undefined risk of malignancy and infection associated with new disease-modifying therapies without long-term safety data comorbidities, adverse health behaviors, and potential interactions of the DMT with concomitant medications. B Show 6 more Disease-modifying therapies, choice of agent, relapsing-remitting MS: As per MENACTRIMS 2020 guidelines, consider initiating the following disease-modifying therapies in treatment-na ve patients: interferon beta glatiramer acetate teriflunomide dimethyl fumarate. E Show 4 more As per AAN 2018 guidelines, initiate the following agents in patients with highly active MS: alemtuzumab fingolimod natalizumab. B Show 3 more As per EAN/ECTRIMS 2018 guidelines, initiate the following drugs in patients with active relapsing-remitting MS, with the choice of agent depending on patient characteristics and https://web.pathway.md/diseases/recUn6IGFcair5i4r 4/13 6/30/23, 1:06 AM Multiple sclerosis Pathway comorbidities, disease severity/activity, drug safety profile, and accessibility of the drug, decided in discussion with the patient: interferon -1b, interferon -1a (SC, IM) peginterferon -1a glatiramer acetate teriflunomide dimethyl fumarate cladribine fingolimod daclizumab, natalizumab, ocrelizumab, alemtuzumab. E Disease-modifying therapies, choice of agent, primary-progressive MS: As per AAN 2018 guidelines, initiate ocrelizumab in patients with primary progressive MS likely to benefit from this therapy unless there are risks of treatment that outweigh the benefits. B As per EAN/ECTRIMS 2018 guidelines, consider initiating ocrelizumab in patients with primary- progressive MS. C Disease-modifying therapies, choice of agent, secondary-progressive MS: As per MENACTRIMS 2020 guidelines, consider initiating a trial of cyclophosphamide, methotrexate, or mycophenolate in patients with rapidly progressive secondary-progressive MS not responding to ocrelizumab or siponimod or having no access to these medications. E As per EAN/ECTRIMS 2018 guidelines, consider initiating interferon-1a (SC) or interferon-1b in patients with active secondary-progressive MS, taking into account the dubious efficacy, as well as the safety and tolerability profile of these drugs, in discussion with the patient. C Show 2 more Disease-modifying therapies, switching to another agent: As per AAN 2018 guidelines, consider switching to another DMT in patients with MS experiencing 1 relapse, 2 unequivocally new MRI-detected lesions, or increased disability on examination on a DMT long enough (> 1 year) for the treatment to take full effect and being adherent to their therapy. C Show 10 more As per EAN/ECTRIMS 2018 guidelines, consider continuing a disease-modifying drug if the patient is stable (clinically and on MRI) and shows no safety or tolerability issues. C Show 3 more Disease-modifying therapies, discontinuation: As per AAN 2018 guidelines, counsel patients with relapsing-remitting MS being stable on DMT and wishing to discontinue therapy regarding the need for ongoing follow-up and periodic reevaluation of the decision to discontinue DMT. B Show 5 more As per EAN/ECTRIMS 2018 guidelines, take into consideration the possibility of resumed disease activity or even rebound when discontinuing treatment, particularly with natalizumab. B https://web.pathway.md/diseases/recUn6IGFcair5i4r 5/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Management of spasticity (exercise): consider advising exercising to reduce spasticity in patients with severe MS. C Management of spasticity (skeletal muscle relaxants): Consider offering oral or intrathecal baclofen, C tizanidine, C and GABAergic drugs to reduce spasticity in patients with MS, taking into account the presence of other symptoms and possible adverse events. C Avoid offering benzodiazepines to reduce spasticity in patients with severe MS because of insufficient evidence for efficacy and frequent adverse events. D Management of spasticity, cannabinoids: As per CCP-CEG 2023 guidelines, offer cannabinoid-based medicines as an adjunct to muscle spasm management in patients with MS not achieving adequate response with other modalities. B As per EAN 2020 guidelines, offer nabiximols to reduce spasticity in patients with severe MS, taking into account drug availability, the presence of other symptoms, and possible adverse events. B Consider offering other cannabinoids, such as D9-tetrahydrocannabinol or cannabis sativa plant extract, to reduce spasticity in patients with severe MS, taking into account drug availability, the presence of other symptoms, and possible adverse events. B As per AAN 2014 guidelines: Consider offering oral cannabis extract, B tetrahydrocannabinol, or oromucosal cannabinoid spray nabiximols to reduce patient-reported symptoms of spasticity in patients with MS. C Avoid offering oromucosal cannabinoid spray to reduce MS-related tremor. D Management of spasticity, botulinum toxin: As per EAN 2020 guidelines, consider offering botulinum toxin A to reduce hip adductor spasticity in patients with severe MS, taking into account the presence of other symptoms and possible adverse events. C As per AAN 2016 guidelines, offer onabotulinumtoxin A or abobotulinumtoxin A for focal manifestations of adult spasticity involving the lower limb warranting treatment. A Show 2 more Management of spasticity (transcutaneous electrical nerve stimulation): consider offering transcutaneous electrical nerve stimulation to reduce spasticity in patients with severe MS. C Management of pain, anticonvulsants and antidepressants: As per EAN 2020 guidelines: Consider offering gabapentin, pregabalin, amitriptyline, duloxetine, or lamotrigine to reduce pain in patients with severe MS. C Consider offering carbamazepine or oxcarbazepine in patients with severe MS and trigeminal neuralgia. Consider offering lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen, and phenytoin, either alone or as add-on therapy, as second-choice therapy. C As per EFNS 2010 guidelines, offer pregabalin, A amitriptyline, B or gabapentin A as first- line therapy for central neuropathic pain. A https://web.pathway.md/diseases/recUn6IGFcair5i4r 6/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Management of pain, opioids: As per EAN 2020 guidelines, consider offering opioids for pain management if long-term pain treatment is not an issue. C As per EFNS 2010 guidelines, consider offering tramadol as second-line therapy for central neuropathic pain. Offer strong opioids as second- or third-line therapy if chronic treatment is not an issue. C Management of pain, cannabinoids: As per CCP-CEG 2023 guidelines, offer cannabinoid-based medicines as an adjunct to pain management in patients with MS not achieving adequate response with other modalities. B As per EAN 2020 guidelines, consider offering cannabinoids (D9-tetrahydrocannabinol, cannabis sativa plant extract, or nabiximols) to reduce pain in patients with severe MS. C As per AAN 2014 guidelines, consider offering oral cannabis extract to reduce patient-reported symptoms of pain (excluding central neuropathic pain) in patients with MS. B Show 2 more As per EFNS 2010 guidelines, consider offering cannabinoids for pain management in patients with MS only if all other treatments fail. B Management of pain (therapeutic procedures): Consider offering radial shock wave therapy C or transcutaneous electrical nerve stimulation, preferably 8-hour application time, to reduce pain in patients with severe MS. C Consider offering surgery in patients with severe MS and trigeminal neuralgia if medical treatment is ineffective or poorly tolerated. C Management of fatigue (nonpharmacological management): Offer exercise training to treat fatigue in patients with severe MS, including robot-assisted gait training, inspiratory muscle training, upper body endurance training, and manual wheelchair propulsion training, taking into account patient preferences and the setting and availability of the apparatus. B Consider offering mindfulness-based training, CBT, fatigue management programs, or other exercise training to treat fatigue in patients with severe MS, taking into account patient preferences and the setting and availability of the program. C Management of fatigue (pharmacotherapy): consider offering amantadine to treat fatigue in patients with severe MS. C Show 2 more Management of urinary incontinence (antimuscarinic agents): consider offering antimuscarinic drugs to improve urinary continence in patients with severe MS, taking into account the presence of other symptoms (such as cognitive problems) and possible adverse events when deciding on the preparation, dose, and route of administration. C Management of urinary incontinence (desmopressin): consider offering desmopressin intranasal spray for nocturia in patients with severe MS. Do not offer desmopressin intranasal spray in patients with uncontrolled hypertension and cardiovascular and/or renal diseases. C https://web.pathway.md/diseases/recUn6IGFcair5i4r 7/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Management of urinary incontinence, cannabinoids: As per EAN 2020 guidelines: Consider offering D9-tetrahydrocannabinol or cannabis extract to improve urinary continence in patients with severe MS, taking into account drug availability, the presence of other symptoms, and possible adverse events. C Insufficient evidence to support the use of nabiximols to improve urinary continence in patients with severe MS. I As per AAN 2014 guidelines, consider offering oromucosal cannabinoid spray (nabiximols), where available, to reduce symptoms of urinary frequency in patients with MS. C Management of urinary incontinence (botulinum toxin): consider offering intradetrusor injections of botulinum toxin A in patients with severe MS if antimuscarinic drugs have proved to be ineffective or poorly tolerated. C Management of urinary incontinence (behavioral management): consider offering behavioral management programs, such as timed voiding, bladder retraining, or habit retraining, to improve urinary continence in patients with severe MS. C Management of urinary incontinence (pelvic floor muscle training): consider offering pelvic floor muscle training, alone or in combination with biofeedback, to improve urinary continence in patients with severe MS. C Management of urinary incontinence (catheterization): Consider teaching clean intermittent self-catheterization in patients with severe MS with a persistent residual volume > 100 mL. Consider training a patient carer to catheterize if self- catheterization is not possible. C Consider offering a long-term indwelling catheter (preferably suprapubic) if clean intermittent (self-)catheterization is no longer possible. C Management of deppressive symptoms: consider offering individual telephone-administered CBT for 16 weeks for depressive symptoms in patients with MS. C Show 2 more Management of pseudobulbar affect: consider offering dextromethorphan/quinidine for the management of pseudobulbar affect in patients with MS. C Management of sleep disturbances (CEG-CCP): offer cannabinoid-based medicines as an adjunct to sleep disorder management in patients with MS not achieving adequate response with other modalities. B Management of sleep disturbances: as per AASM 2021 guidelines, consider offering modafinil for the treatment of adult patients with hypersomnia secondary to MS. C Palliative care: consider offering home-based palliative care, either by healthcare professionals with good basic palliative care skills and knowledge or by multi-professional teams of palliative care specialists, in patients with severe MS. C Show 4 more https://web.pathway.md/diseases/recUn6IGFcair5i4r 8/13 6/30/23, 1:06 AM Multiple sclerosis Pathway 4. Nonpharmacologic interventions Support programs: consider directing patients with MS eligible for disease-modifying therapies to support programs. C Alternative and complementary therapies: Consider counseling patients with MS regarding the following: ginkgo biloba is ineffective for improving cognitive function B but is possibly effective for reducing fatigue C a low-fat diet with fish oil supplementation is probably ineffective for reducing relapses, disability, or MRI lesions, or for improving fatigue or quality of life in MS C lofepramine plus L-phenylalanine with vitamin B12, i.e. Cari Loder regimen, is possibly ineffective for treating disability, symptoms, depression, or fatigue C reflexology is possibly effective for reducing paresthesia C bee sting therapy is possibly ineffective for reducing relapses, disability, fatigue, total MRI lesion burden, new gadolinium-enhancing lesion volume, or health-related quality of life C magnetic therapy is probably effective for reducing fatigue and probably ineffective for reducing depression C the safety and efficacy of other reviewed complementary and alternative medicine or the interaction of complementary and alternative medicine with disease-modifying therapies for MS are unknown. C 5. Specific circumstances Pregnant patients: As per AAN 2018 guidelines, monitor the reproductive plans of females of childbearing potential with MS, and counsel patients on DMT regarding reproductive risks and the use of contraception. B Show 3 more As per EAN 2018 guidelines, consider initiating interferon or glatiramer acetate until pregnancy is confirmed in female patients planning a pregnancy and having a high risk of disease reactivation. Consider continuing this treatment during pregnancy in selected very specific (active) cases. C Show 3 more 6. Preventative measures Routine immunizations: discuss the evidence regarding immunizations in MS with the patient and explore their opinions, preferences, and questions. B Show 6 more https://web.pathway.md/diseases/recUn6IGFcair5i4r 9/13 6/30/23, 1:06 AM Multiple sclerosis Pathway 7. Follow-up and surveillance Assessment of treatment response: As per AAN 2018 guidelines, monitor for medication adherence, adverse effects, safety, and effectiveness of the DMT in patients with MS on disease-modifying therapies. B Show 3 more As per EAN 2018 guidelines, consider combining MRI with clinical measures when evaluating disease evolution in treated patients. C Show 3 more Clinical findings Patient demographics Symptoms Female sex Anxiety Depression Past medical history Double vision Dysesthesia Diabetes mellitus type 1 Dysphagia EBV infection Eye pain IBD Facial hypoesthesia Obesity Facial numbness Optic neuritis Facial pain Psoriasis Facial weakness Restless leg syndrome Fatigue Transverse myelitis Fecal incontinence Vitamin D deficiency Gait disturbance Neurological exam Hypoesthesia Limb weakness Ataxia Low sex drive Charcot's neurologic triad Muscle spasms Cognitive impairment Muscle weakness Dysarthria Numbness Hemiparesis Painful eye movements Internuclear ophthalmoplegia Paresthesia Limb paresis Sleeping disorder Neck stiffness Tingling Nystagmus Urinary incontinence Paraparesis Vertigo Speech disturbance Vision loss Tremor Visual disturbances Lhermitte's phenomenon Uhthoff's phenomenon Social history https://web.pathway.md/diseases/recUn6IGFcair5i4r 10/13 6/30/23, 1:06 AM Multiple sclerosis Pathway Tobacco use Imaging findings Ocular exam Central vein sign Dawson's fingers Binocular diplopia Ependymal "Dot-Dash" sign Oscillopsia Open ring sign Relative afferent pupillary defect T1 black holes visual acuity References 1. D S Goodin, E M Frohman, G P Garmany 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. Open 2. F Sellebjerg, D Barnes, G Filippini et al. EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. Eur J Neurol. 2005 Dec;12 12 939 46. Open 3. Xavier Montalban, Ralf Gold, Alan J Thompson et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018 Feb;24 2 96 120. Open 4. A Solari, A Giordano, J Sastre-Garriga et al. EAN guideline on palliative care of people with severe, progressive multiple sclerosis. Eur J Neurol. 2020 Aug;27 8 1510 1529. Open 5. N Attal, G Cruccu, R Baron et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010 Sep;17 9 1113-e88. Open 6. Lichtenstein GR, Loftus EV, Isaacs KL et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018 Apr;113 4 481 517. Open 7. B Yamout, M Sahraian, S Bohlega et al. Consensus recommendations for the diagnosis and treatment of multiple sclerosis: 2019 revisions to the MENACTRIMS guidelines. Mult Scler Relat Disord. 2020 Jan;37 101459. Open 8. Yadav V, Bever C Jr, Bowen J et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014 Mar 25;82 12 1083 92. Open 9. 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. Open 10. Minden SL, Feinstein A, Kalb RC et al. Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Jan 14;82 2 174 81. Open 11. Paul M Lantos, Jeffrey Rumbaugh, Linda K Bockenstedt et al. Clinical Practice Guidelines by the Infectious Diseases Society of America IDSA , American Academy of Neurology AAN , and American College of Rheumatology ACR 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease. Arthritis Care Res Hoboken). 2021 Jan;73 1 1 9. Open https://web.pathway.md/diseases/recUn6IGFcair5i4r 11/13 6/30/23, 1:06 AM Multiple sclerosis Pathway 12. Kiran Maski, Lynn Marie Trotti, Suresh Kotagal et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021 Sep 1;17 9 1881 1893. Open 13. Alan D Bell, Caroline MacCallum, Shari Margolese et al. Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions. Cannabis Cannabinoid Res. 2023 Mar 27. Open 14. Edgar Carnero Contentti, Juan Ignacio Rojas, Edgardo Cristiano et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord. 2020 Oct;45 102428. Open 15. Simpson DM, Hallett M, Ashman EJ et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10;86 19 1818 26. Open 16. Jolien Schol, Lucas Wauters, Ram Dickman et al. United European Gastroenterology UEG and European Society for Neurogastroenterology and Motility ESNM consensus on gastroparesis. United European Gastroenterol J. 2021 Apr;9 3 287 306. Open 17. Farez MF, Correale 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. 2019 Sep 24;93 13 584 594. Open 18. Expert Panel on Neurological Imaging, Vikas Agarwal, Lubdha M Shah et al. ACR Appropriateness Criteria Myelopathy: 2021 Update. J Am Coll Radiol. 2021 May;18 5S S73 S82. Open 19. Dilokthornsakul P, Valuck RJ, Nair KV et al. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016 Mar 15;86 11 1014 21. Open 20. Daltrozzo T, Hapfelmeier A, Donnachie E et al. A Systematic Assessment of Prevalence, Incidence and Regional Distribution of Multiple Sclerosis in Bavaria From 2006 to 2015. Front Neurol. 2018 Oct 30;9 871. Open 21. Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018 Jan 11;378 2 169 180. Open 22. Doshi A, Chataway J. Multiple sclerosis, a treatable disease. Clin Med Lond). 2016 Dec;16 Suppl 6):s53-s59. Open 23. Love S. Demyelinating diseases. J Clin Pathol. 2006 Nov;59 11 1151 9. Open 24. Farez MF, Correale 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. 2019 Sep 24;93 13 584 594. Open 25. M J Hohol, E J Orav, H L Weiner. Disease steps in multiple sclerosis: a simple approach to evaluate disease progression. Neurology. 1995 Feb;45 2 251 5. Open 26. Anand Padmanabhan, Laura Connelly-Smith, Nicole Aqui et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34 3 171 354. Open https://web.pathway.md/diseases/recUn6IGFcair5i4r 12/13 6/30/23, 1:06 AM Multiple sclerosis Pathway 27. Theresa A Zesiewicz, George Wilmot, Sheng-Han Kuo et al. Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Mar 6;90 10 464 471. Open https://web.pathway.md/diseases/recUn6IGFcair5i4r 13/13