Where Does Multiple Sclerosis Usually Start? Early Signs Explained

Multiple Sclerosis (MS) the prototypical inflammatory demyelinating disease of the central nervous system is defined as intermittent neurologic dysfunction at least twice separated in time and space. Thus, the typical presentation of MS is considered the first attack of MS.

Key takeaways:
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    While there are no specific signs and symptoms of MS, it is typically seen with well-defined presentations.
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    Most common presentation of MS would be a white middle-aged woman with temporary visual or sensory loss, i.e., optic neuritis or transverse myelitis.
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    The first episode suggestive of MS is termed the clinically isolated syndrome (CIS), though not all CIS diagnoses progress to a full MS diagnosis.
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    Sometimes, incidental imaging elucidates MS findings in patients without signs and symptoms, termed Radiologically Isolated Syndrome, however, as in CIS, not all cases will progress to MS.

Common Presentation of MS

MS has been typically expected to present in a middle-aged white woman complaining of temporary visual or sensory loss. As such the most common presentation of MS is optic neuritis and transverse myelitis.

However, MS can afflict any gender, sex or age with carriable neurologic symptoms. Cerebellar ataxia and/or sensory complaints are also common upon initial presentation. Some patients with MS may present initially with a progressive course, with foot drop or other spastic paraplegias.

Yet another group of patients in the context of initial diagnosis of MS may have subtle changes in vision, reflexes, ambulation that may be evidence of previous attacks, that may have been ignored or not noticed by the patient.

Finally, some patients have also reported depression, cognitive decline or psychosis and thus MS should be considered in the differential diagnoses of such presentations, albeit rare.

Clinical Findings in MS

There are no clinical symptoms or signs that are unique or pathognomonic of MS, however there are some that are most typical.

Some features typically suggestive of MS are:

  • Relapses and Remissions.
  • Age of onset between 15 and 45 years of age.
  • Optic Neuritis.
  • Lhermitte Sign.
  • Fatigue.
  • Uhthoff Phenomenon (Heat Sensitivity).

While some features considered atypical for MS are:

  • Steady progression.
  • Age of onset in childhood or after 50 years of age.
  • Cortical deficits presenting with aphasia, apraxia or neglect.
  • Rigidity or dystonia.
  • Seizures.
  • Early onset dementia.
  • Sudden onset of deficits (within minutes).

Research has demonstrated that in patients diagnosed with MS, 31% had sensory complaints in their extremities, 16% had visual loss, while around 10% each had motor deficits, gait disturbance, balance problems or diplopia. Lhermitte sign, electric shock sensations running down one’s neck upon flexion of the neck, once considered almost pathognomonic for MS was rare with only 2% of the patients initially presenting with it.

Clinically Isolated Syndrome (CIS)

A clinically isolated syndrome (CIS) is considered the first clinical episode that likely indicates MS. It is typically characterized by:

  • Applicable signs and symptoms explained by a demyelinating event in the CNS.
  • Acute or subacute development with a duration of at least 24 hours with or without recovery.
  • Absence of fever and/or infection.
  • Resemblance to a typical MS attack in a patient not previously diagnosed with MS.

In such an attack, the typical presentations are:

  • One sided optic neuritis, painful visual loss in one eye either with scotoma or visual blurring.
  • Painless diplopia due to internuclear ophthalmoplegia or a 6th Cranial Nerve Palsy.
  • A brainstem or cerebellar syndrome either consisting of diplopia, or ataxia with gaze-evoked nystagmus, vertigo, facial numbness or dysarthria that is sometimes paroxysmal.
  • Partial transverse myelitis, with predominant sensory complaints such as partial Brown-Sequard Syndrome, Lhermitte sign, or bladder and/or bowel involvement with urge incontinence as well as Erectile Dysfunction.

Symptoms of such an attack would be expected to develop over hours to days and remit over weeks to months, though not always fully. CIS is thought to be a precursor and not all patients diagnosed with CIS will progress to a full MS diagnosis.

Of note, CIS can present with either a single focused symptom or symptoms explained by multiple foci, depending on the number of lesions.

Radiologically Isolated Syndrome

In rare cases, an incidental Cerebral or Spinal Cord MRI (one ordered for other unrelated conditions such as trauma) can portend findings that would be attributable to MS in the context of lack of any signs or symptoms. Not all patients with such imaging findings would be expected to progress to a diagnosis of MS, however, risk factors for conversion include a younger age of less than 35, male sex as well as lesions on the spinal cord vs. the brain.


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