14B. Diagnosis of multiple sclerosis (+ treatment)

Page created on June 3, 2021. Last updated on April 6, 2022 at 13:40

Diagnosis

Introduction

The diagnosis of multiple sclerosis is based on the McDonald criteria. They require the patient to have evidence of lesions in the CNS in different places and at different times. This is called “dissemination in space” and “dissemination in time”.

In some patients, the diagnosis can be made after a single attack, if they have evidence of dissemination in both space and time. However, in most patients the diagnosis is made after the patient has had multiple attacks. If the diagnosis cannot be made (yet) after a single attack that attack is known as a “clinically isolated syndrome” (CIS). Most likely the patient will later develop another attack, at which point the diagnosis can be made.

Many modalities are used in the diagnosis:

  • MRI with and without gadolinium contrast – shows demyelinating lesions in predilected areas
    • Periventricular white matter, corpus callosum, spinal cord, cerebellum
  • Lumbar puncture – shows oligoclonal bands in CSF
  • Visually evoked potentials (VEP) – shows slowed optic nerve conduction
  • Motor evoked potentials (MEP) – shows dysfunction of pyramidal tract

Dissemination in space

Dissemination in space is evidenced when either of the following apply:

  • Lesions on MRI in two MS-typical regions in the CNS
  • Development of two or more clinical attacks which correspond to different locations in the CNS

Dissemination in time

Dissemination in time is evidenced when either of the following apply:

  • Development of an additional clinical attack
    • (Development of a new relapse after a remission)
  • Presence of both gadolinium-enhancing and non-enhancing lesions on a gadolinium contrast MRI
    • Gadolinium-enhancing lesions are maximum a few weeks old, while non-enhancing lesions are older than that
  • Presence of a new gadolinium-enhancing lesion on a follow-up contrast MRI

Presence of oligoclonal bands in CSF can act as a criteria of dissemination in time, even though it’s not strictly a sign of dissemination in time.

Differential diagnosis

  • Migraine
  • Neuromyelitis optica
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Behcet disease
  • Neuroborreliosis
  • Neurosyphilis

Neuromyelitis optica has similar symptoms as MS but worse prognosis and different treatment, so important to distinguish them. NMOD has normal brain MRI, no oligoclonal bands, etc.

Treatment

Not part of the topic in neuro 2, but it’s a topic on the final.

Introduction

Modern treatment for MS has increased the average lifespan of people with MS. It’s important to initiate treatment early. We can divide MS-treatment in three categories: acute treatment of attacks, disease-modifying treatment, and symptomatic treatment.

Acute treatment

Acute treatment hastens time to recovery, but does not improve long-term disability or decrease risk of subsequent attacks.

The first line treatment of MS attacks is methylprednisolone either p.o. or i.v., usually 1000 – 1200 mg daily for 3 – 5 days. PPI should be added if there is high risk for ulcer. Second line is IVIG or plasma exchange.

Treatment is indicated only for true MS attacks, i.e. they must last > 24 hours and occur in the absence of fever or infection.

Disease-modifying treatment

Disease-modifying treatment decreases the risk for relapse. There are many drugs available, some with higher efficacy than others:

  • Highest efficacy
    • Rituximab
    • Cladribine
    • Ozanimod
    • Alemtuzumab
    • Ponesimod
    • Natalizumab
  • Intermediate efficacy
    • Fingolimod
    • Dimethyl fumarate
  • Lowest efficacy
    • Interferon
    • Glatirame acetate
    • Teriflunomide

Some advocate for beginning with lowest efficiency drugs and stepping up if needed, but most agree that beginning with highest efficiency drugs is best. Most are administered intravenously, but some are orally administered (fingolimod, teriflunomide, dimethyl fumarate). Many women with MS are in fertile age and so potential teratotoxicity and safety during pregnancy must be taken into account.

Symptomatic treatment

There are many options for treatment of MS symptoms, both pharmacological and non-pharmacological:

  • Gait problems – fampiridin, physiotherapy, exercise
  • Spasticity – baclofen, cannabidiol, botulinum toxin injection, physiotherapy
  • Neuropathic pain – antiepileptics, TCA, SNRI
  • Cerebellar ataxia – physiotherapy
  • Dysphagia – speech therapy
  • Bladder disturbances – depends on type. Kegel exercises, antimuscarinic drugs, intermittent catheterisation
  • GI symptoms (constipation, incontinence) – fiber intake, exercise, laxatives
  • Sexual problems – sildenafil, sexual aids
  • Depression, anxiety – psychotherapy, antidepressants
  • Insomnia – sleep hygiene, CBT, Z-drugs

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