Multiple sclerosis resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D., Fahimeh Shojaei, M.D.

Synonyms and keywords:Multiple sclerosis management, Multiple sclerosis workup, Multiple sclerosis approaches, approach to Multiple sclerosis, Multiple sclerosis treatment

Overview

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system and it’s known to be multi-factorial. The onset of symptoms are mostly between the age of fifteen to forty years (rarely before age fifteen or after age sixty), and include fatigue, mood problems, spasticity, bowel and bladder dysfunction, cognitive impairment, eye movement problems, heat sensitivity, incoordination, pain, sexual dysfunction, sleep disorder, vertigo and visual loss. There is no single diagnostic study of choice for Multiple sclerosis. Diagnosis is currently made by the fulfilment of the McDonald criteria, which include clinical presentation, cerebral plaques on MRI , and oligoclonal bands in CSF analysis. Treatment for multiple sclerosis includes disease-modifying medications (DMTs) and immunosuppressors to prevent relapses and Glucocorticoid therapy in acute exacerbations.

Causes

Life-Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• There are no life-threatening or permanent disabiling causes for Multiple sclerosis if left untreated within 24 hours.

Common Causes

• Autoimmunity:
  • Autoreactive T cells
  • Myelin basic protein-specific CD4+ T cells
• Infectious:
  • Epstein-Barr virus
  • Chlamydia
  • Herpes virus
• Degeneration:
  • Axonal degeneration
  • Cortical atrophy

Diagnosis

The diagnostic criteria for multiple sclerosis is 2017 McDonald criteria:

Clinical presentation	Additional Data Needed
2 or more attacks (relapses) 2 or more objective clinical lesions	None; clinical evidence will suffice (additional evidence desirable but must be consistent with MS)
2 or more attacks 1 objective clinical lesion	New criteria: Dissemination in space, demonstrated by: MRI Further clinical attack involving different site Presence of 1 or more T2 lesions in at least 2 of 4 of the following areas of the CNS: Periventricular, Juxtacortical, Infratentorial, or spinal cord
1 attack 2 or more objective clinical lesions	Dissemination in time (DIT), demonstrated by: MRI Second clinical attack New criteria: No longer a need to have separate MRIs run; dissemination in time, demonstrated by: simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time; or A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or await a second clinical attack. [This allows for quicker diagnosis without sacrificing specificity, while improving sensitivity]
1 attack 1 objective clinical lesion (clinically isolated syndrome)	New criteria: Dissemination in space and time, demonstrated by: For DIS: 1 or more T2 lesion in at least 2 of 4 MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord); or await a second clinical attack implicating a different CNS site; and for DIT: simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time; or a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan; or await a second clinical attack.
Insidious neurological progression suggestive of MS (primary progressive MS)	New criteria: One year of disease progression (retrospectively or prospectively determined) and two or three of the following: Evidence for DIS in the brain based on 1 or more T2 lesions in the MS-characteristic (periventricular, juxtacortical, or infratentorial) regions Evidence for DIS in the spinal cord based on 2 or more T2 lesions in the cord

Treatment

Shown below is an algorithm summarizing the treatment of Multiple sclerosis according the the NHS England’s Neuroscience Clinical Reference Group guidelines:

Single clinical episode suggestive of MS

Without MRI abnormalities

With MRI abnormalities and fulfilling the McDonald criteria

Do not treat

Fulfills the definition of Clinically Isolated Syndrome (CIS)

Patient with relapsing-remitting MS

Radiological markers indicative of a poor prognosis for rapidly developing permanent disability

Do not treat

Interferon beta 1a or glatiramer acetate

Alemtuzumab or Ocrelizumab

Relapse

2 significant relapses in last 2 years

Plasmapheresis

Alemtuzumab or Ocrelizumab

Poor response

Steroids

Severe relapse or contraindications to high dose-steroids

Natalizumab

Positive John Cunningham (JC) virus

Close MRI follow-up or change to Cladribine

Dos

• If patient presents with clinical isolated sindrome (CIS), recommend serial imaging at least annually for the first 5 years and close follow-up rather than initiating DMT.
• Counsel patients with newly diagnosed MS about specific treatment options with DMT, side effects, and reproductive plans at a dedicated treatment visit.
• In the presence of a relapse, do not waste time to give steroids; plasma exchange may be necessary in case of an acute-severe setting or when there is contraindications to high-dose corticosteroids.
• Cladribine and the monoclonal antibody therapies should be discussed by a multi-disciplinary team (MDT) meeting, defined as a minimum of at least two specialist consultant neurologists plus at least one specialist MS nurse, with access to neuro-radiology expertise.
• Perform follow-up MRIs in patients with anti-JCV antibody positive status using Natalizumab. Natalizumab may be changed to Cladribine or Fingolimod if treatment duration exceeds 2 years or the patient is in a immunosuppressant state.
• Indicate six weeks of comprehensive multidisciplinary outpatient rehabilitation, since it has shown to be effective for improving disability/function.

Don'ts

• Do not continue disease modifying therapy if adverse effects of the drug are observed, the patient becomes pregnant or they develop progressive disease or fixed disability above EDSS 6.5.
• Do not prescribe mitoxantrone to people with MS unless the potential therapeutic benefits greatly outweigh the risks, due to high frequency of severe adverse effects.