• Clinical science

Multiple sclerosis


Multiple sclerosis (MS) is a chronic, degenerative disease of the CNS that is caused by an immune-mediated inflammatory process. This process results in the demyelination of white matter in the brain and spinal cord. MS has a higher prevalence among women and people in temperate regions such as Europe and North America. Impaired vision (due to retrobulbar neuritis) is usually the first manifestation of the disease. Other neurological deficits also appear as the disease progresses. The most common clinical course is characterized by exacerbations (relapses) followed by periods of complete/incomplete remission. MRI, which is the investigation of choice, reveals demyelinated sclerotic plaques in white matter. Differential diagnosis of MS includes other chronic demyelinating diseases and neurological infections (e.g., borreliosis, neurosyphilis). Acute exacerbations of MS are treated with high-dose glucocorticoids. Between relapses, patients may be treated with disease-modifying drugs (e.g., β-interferon, glatiramer acetate). No definitive therapy is available for MS.


  • Sex: > (2:1)
  • Age of onset: 20–40 years of age
  • Ethnicity: prevalence among the white population
  • Prevalence is greater among people in temperate zones.

MS is more common in women!


Epidemiological data refers to the US, unless otherwise specified.


  • Unclear
  • Genetic predisposition
    • 35% disease concordance among monozygotic twins
    • 3–4% disease concordance among first-degree relatives
  • Environmental triggers
    • UV radiation, insufficient vitamin D consumption, cigarette smoking
    • Pathogens: EBV, HHV 6



  • Immune-mediated damage
    • Exact cause remains unknown
    • Characterized by inflammation, demyelination, and axonal degeneration
    • Most commonly accepted theory: Activation of autoreactive T-lymphocytes → inflammatory processes → focal demyelination with partial preservation of axons (acute plaques) → loss of axons and atrophy of oligodendrocytes (chronic plaques)gliosis → inadequate remyelination
    • There is evidence for Th1 immune response involving myelin basic proteins
    • Disturbed B-lymphocyte function: The pathogenetic role of B-lymphocytes is unclear but is supported by the following findings in MS patients:
  • Most common sites of demyelination in MS
    1. Periventricular areas
    2. Brainstem
    3. Cerebellum
    4. Spinal cord


Clinical features

In 60% of cases of optic neuritis, fundoscopy is normal. Neither the patient nor doctor are able to see anything!

Uhthoff's phenomenon triggered by a viral infection can be confused with an exacerbation of MS!



Clinical course

Characteristics Incidence at the time of diagnosis
Relapsing-remitting MS (RR-MS)
  • Exacerbations occur
  • Symptoms remit almost completely between exacerbations
  • 90%
Secondary progressive MS (SP-MS)
  • Exacerbations occur
  • Continuous worsening of symptoms in between exacerbations
  • Arises from RR-MS (as per definition)
Primary progressive MS (PP-MS)
  • No exacerbations
  • Continuous worsening of symptoms from the very onset of the disease
  • 10%
Definition of relapse/exacerbation: new symptoms or significant worsening of existing symptoms, both of which last at least 24 hours and are preceded by at least 30 days of relative clinical stability.

Special forms of MS

  • Clinically isolated syndrome (CIS): used to describe a constellation of neurological symptoms that might in hindsight be the first episode of MS
  • Diffuse cerebral sclerosis (Schilder's disease)
    • Clinical course: primarily affects children; monophasic course with most patients dying within 1–2 years of disease onset
    • Clinical features: large areas of demyelination → various neurological deficits and psychological changes

Expanded Disability Status Scale (EDSS)

EDSS grades the severity of disability caused by MS. The following systems are individually evaluated and given a score (functional systems score, FSS):

The net score is used to grade the patient's disability on the EDSS:

Key points on the scale
0–3.5 No/mild changes in up to two functional systems
> 4.0 Limited mobility
7.0 Confined to a wheelchair (complete immobility)
10 Death



Instrument-based diagnostics

  • Plain MRI (brain and spine): investigation of choice
    • Multiple sclerotic plaques (most commonly seen in periventricular white matter) with finger-like radial extensions (Dawson's fingers)
    • Contrast MRI (with gadolinium): enhancement of active lesion during and up to 6 weeks after the exacerbation
    • In T1: hypo-/isointense; severe demyelination and axonal destruction → black hole lesions
    • In T2 und FLAIR : hyperintense
  • Electrophysiological studies: slowed nerve conduction → increased latency of visually evoked potentials (VEP)
  • For more detailed information, see McDonald's criteria.

Lumbar puncture for CSF examination

The appearance of oligoclonal bands in the early stages of the disease indicates a poor prognosis!


Revised McDonald's criteria

Number of exacerbations Number of clinical manifestations Additional criteria for diagnosis of MS
≥2 ≥2
  • No additional evidence is required! Clinical evidence is sufficient for the diagnosis of MS.
  • Either of the following criteria:
    1. Spatial dissemination on MRI scans
    2. Positive CSF findings and 2 or more lesions on MRI scans suggestive of MS
1 ≥2
  • Spatial dissemination on MRI (simplified definition): evidence of at least one lesion on T2-weighted imaging in at least 2 of the following CNS regions: periventricular, juxtacortical, infratentorial, spinal
  • Temporal dissemination on MRI is defined by any one of the following criteria:
    1. Evidence of an asymptomatic, gadolinium-enhanced lesion on the first MRI scan
    2. Evidence of a new lesion on T2-weighted imaging or a new gadolinium-enhanced lesion that was not present on the first MRI scan


Differential diagnoses

Autoimmune diseases



The differential diagnoses listed here are not exhaustive.


Summary of step-wise therapy for multiple sclerosis

  • The goal is to begin treatment as early as possible to treat the primary exacerbation, prevent further exacerbations, and slow down the disease process.
  • Therapeutic strategies include
    • Escalation therapy: Patients who do not respond to first-line therapy with disease-modifying drugs (DMDs), are switched to second-line DMDs.
    • Induction therapy: Patients with severe disease activity at onset, first receive strong immunosuppressant drugs , followed by long-term maintenance therapy with DMDs.
Summary of multiple sclerosis therapy
Indication Clinically isolated syndrome (CIS) Relapsing remitting MS (RR-MS) Secondary progressive MS (SP-MS) Primary progressive MS (PP-MS)
Treatment of acute exacerbation
  • No exacerbations present
Prevention of exacerbations
  • There is no established therapy for PP-MS
  • Supportive therapy is essential.

Treatment of acute exacerbations

Disease-modifying MS therapy (prevention of exacerbations)

Disease-modifying drugs (DMDs)
Medication Mechanism of action Route of application Indications Side effects

Interferon beta

  • First-line drug in all forms of MS
  • Injection site necrosis
  • Flu-like symptoms
  • Liver dysfunction
  • Thrombotic microangiopathy
  • Depression
Glatiramer acetate (copolymer-1)
Mitoxantrone IV
  • Third-line drug in RR-MS

Dimethyl fumarate
  • An immunomodulator that protects nerve cells through its anti-inflammatory effect
  • First-line drug in RR-MS
  • Inhibits pyrimidine synthesis, which has an antiproliferative and anti-inflammatory effect
  • Less activated lymphocytes enter the CNS
Fingolimod PO
  • First-line drug in RR-MS


  • A monoclonal antibody against the superficial antigen CD52, which is found on the surface of immune cells.(T-cells, B-cells, NKT cells, and monocytes)
  • As a consequence, both B- and T-lymphocytes numbers decrease drastically.
  • Third-line drug in RR-MS
Natalizumab IV
  • Second-line drug in RR-MS

Supportive therapy



Prognostic factors

Favorable factors Unfavorable factors
Disease onset Age of symptom onset < 35 years > 35 years
Symptoms Only sensory symptoms Multiple symptoms with early motor and cerebellar involvement
Exacerbation Duration Short (a few days) Long (several weeks)
Remission Adequate Inadequate
Clinical features Able to walk Early loss of ambulation
Diagnostic findings Imaging

Late-onset lesions

Early-onset, multiple lesions

Electrophysiological studies Late-onset changes Abnormal sensory and motor evoked potentials, which appear early in the course of the disease

Special patient groups

Multiple sclerosis in pregnancy