Diagnosing multiple sclerosis

Click here! Learn how to recognize the signs, symptoms, and disease patterns of multiple sclerosis in your patients.
Last update26th Jan 2021

Multiple sclerosis (MS) is a debilitating disease that most often affects women. The onset of MS usually occurs in the third or fourth decade of life. It involves episodic and localized autoimmune attacks on the myelin sheath of the central nervous system (CNS) neurons. As such, it is classified as a demyelinating disease.

Figure 1. A healthy myelin sheath compared to a damaged myelin sheath. Destruction of the myelin sheath occurs in demyelinating diseases such as multiple sclerosis (MS).

The loss of myelin’s insulation slows conduction through the affected neurons, resulting in dysfunction. The clinical manifestation of the dysfunction depends on the location of the demyelination.

For example, if there is demyelination of an optic nerve, the patient may suffer unilateral visual loss. If demyelination occurs in the spinal cord, they may suffer paresis. If the demyelination occurs in Broca’s area (left frontal lobe), they may exhibit aphasia.

What is the pattern of disease in MS?

Symptoms of MS can be extremely varied, depending on where the areas of demyelination occur within the nervous system. Symptoms usually present as a rapidly progressive loss of a specific function followed by a gradual improvement. After a period of months to years, the patient will experience another attack. The pattern consisting of a loss of function followed by improvement repeats. Each attack tends to occur in another region of the nervous system.

The disease causes demyelination to occur in different areas at different points in time. The patient will experience an attack in one region of the CNS, recover to some degree, and then have another attack in a different location.

Multiple sclerosis can follow various patterns, but most commonly involves periods of disease activity known as relapsing periods and periods of disease quiescence known as remitting periods. In other words, MS is generally relapsing and remitting in nature. Attacks occur during the relapsing periods; improvements and neurological stability occur during the remitting periods.

During the remitting phases, signs and symptoms may go away altogether, or they may persist at a lower intensity. Over time, many patients with MS fall into a progressive variation of the disease where there is less improvement during remission periods and accumulating signs and symptoms from continued relapses.

Figure 2. Multiple sclerosis (MS) has a progressive relapsing-remitting disease course, where patients experience less improvement during remission periods and more signs and symptoms over time from continued relapses.

When should you consider MS as a possible diagnosis?

A definitive diagnosis of MS—particularly early on—can be challenging. Clinical and paraclinical evidence, such as magnetic resonance imaging (MRI), evoked potentials, and lumbar punctures, are generally combined to build a case to explain the combination of multiple neurological syndromes occurring in different areas of the CNS at different times.

Signs and symptoms of MS

There are seven signs and symptoms that are common with MS:

  1. Regions of definitive sensory loss
  2. Visual disturbances (such as double vision or loss of vision)
  3. Definitive weakness (related to a specific region of the CNS)
  4. Hemiparesis or paraparesis
  5. Loss of coordination (such as ataxia or dysmetria)
  6. Vertigo
  7. Bladder dysfunction
Figure 3. Common symptoms of multiple sclerosis (MS) which typically present for more than 24 hours and eventually subside include sensory loss, double vision, visual loss, weakness, hemiparesis or paraparesis, ataxia, dysmetria, vertigo, and bladder dysfunction.

You should consider MS if any of these symptoms are present for more than 24 hours but eventually subside.

Differential diagnosis for MS

When you are considering MS as a diagnosis, many other differentials must be considered:

  • Lupus
  • Lyme disease
  • Vitamin B12 deficiency
  • Acute disseminated encephalomyelitis
  • Syphilis
  • Cerebral vascular diseases
  • Various tumors
  • Human immunodeficiency virus (HIV)
  • Adrenoleukodystrophy
  • Mitochondrial diseases
  • Transverse myelitis
  • Paraneoplastic syndromes
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
  • Leukodystrophies
  • Sarcoidosis
  • CNS vasculitis

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What should you do if you suspect MS?

If you suspect that your patient has MS, ask about a history of any previous neurological events involving flare-ups and remissions that affected other areas of the nervous system. In particular, the events should have occurred in totally different regions of the CNS with totally different symptoms. There should be a history of more than 30 days between separate neurological events.

Figure 4. Multiple sclerosis patients should show a history of separate neurological events that are more than 30 days apart and involve different regions of the central nervous system with totally different symptoms.

Note that optic neuritis (unilateral, painful loss of vision in an eye) is often an early neurological manifestation of MS. As well, ask the patient if hot baths or showers make symptoms worse. Known as Uhthoff’s phenomenon, this is common in individuals with MS.

Perform a thorough neurological exam by looking for evidence of definitive neurological dysfunction elsewhere in the nervous system, in addition to dysfunction related to the current symptoms. For example, look for residual left hemiparesis in addition to the new symptom of acute visual acuity loss.

Additional testing for diagnosing MS

Magnetic resonance imaging

If you are concerned about MS in a patient who has sustained a new, isolated, neurological syndrome, order magnetic resonance imaging (MRI) of the brain with and without contrast. On a T2 MRI, look for scattered spots of high signal in the white matter. These spots may partially enhance, but they do not have to enhance on a post-contrast T1 MRI.

Keep in mind that these spots are not diagnostic for MS by themselves, nor are they conclusive for demyelination in the affected region. Multiple small areas of high signal in white matter regions (particularly near the ventricles) can add to the suspicion of MS, but in no way confirm the diagnosis.

Figure 5. With patients with multiple sclerosis (MS), T2 magnetic resonance imaging (MRI) of the brain will show scattered high signal spots in the white matter, and on post-contrast T1 images, the spots may partially enhance. These findings are not diagnostic for MS but only add to the suspicion of a diagnosis.

Lumbar puncture

A lumbar puncture is sometimes used to support the diagnosis of MS since certain laboratory parameters may be abnormal in these patients. But, there is currently no definitive biomarker for the disease.

There are five lumbar puncture findings that are typical of MS patients:

  1. Normal opening pressure
  2. Normal or mildly elevated cerebrospinal fluid (CSF) protein
  3. Elevated immunoglobulins
  4. Less than 20 mononuclear cells / µL
  5. The presence of oligoclonal bands

Oligoclonal bands on electrophoresis indicate concentrations of certain types of immunoglobulins that are not normally found in the CSF. These are not diagnostic for MS, but if elevated, are highly suggestive of a more aggressive progression of the disease.

Figure 6. Typical lumbar puncture findings in multiple sclerosis patients include a normal opening pressure, normal to mildly elevated cerebrospinal fluid (CSF) protein, elevated immunoglobulins, less than 20 mononuclear cells / µL, and oligoclonal bands.

The McDonald Criteria for diagnosing MS

A definitive diagnosis of MS is often made using the McDonald Criteria, which is a list of diagnostic criteria that is readily available online. The McDonald Criteria looks for evidence of CNS damage disseminated in time and space, combining clinical (history and findings of neurological deficits) and MRI evidence (CNS damage) to make the diagnosis.

Depending on the patient’s presentation, various combinations of evidence are used to make the diagnosis. In a recent revision of the McDonald Criteria, oligoclonal bands in the CSF was added as an indicator of ongoing CNS injury.

There you have it! Use the information here to help you evaluate the possibility of MS in your patient. Then, if you strongly suspect MS, seek neurology input for a definitive diagnosis.

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About the author

Gary R. Simonds, MD MHCDS FAANS
Professor at Virginia Tech School of Neuroscience / Virginia Tech Carilion School of Medicine and Program Director for the Division of Neurosurgery at Virginia Tech Carilion Clinic.
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