History and exam

Key diagnostic factors

common

visual disturbance in one eye

Graying or blurring of vision in one eye (can be described as looking through petroleum jelly). May have pain in moving that eye and describe loss of color discrimination, particularly reds.

peculiar sensory phenomena

Patients often describe odd sensations of a patch of wetness or burning, or hemibody sensory loss or tingling. In particular, banding or hemibanding is associated with spinal cord lesions. Lhermitte sign (electric shock-like sensations extending down the cervical spine radiating to the limbs) and trigeminal neuropathy or neuralgia are other possible sensory findings in MS.

Other diagnostic factors

common

female sex

Female to male sex ratio is approximately 3:1.[10][12]

age 20-40 years

Most commonly diagnosed between ages 20 and 40 years.

foot dragging or slapping

Patient will often describe gradual onset of weakness after walking several blocks or several miles such that the foot slaps the ground. This weakness resolves with rest.

leg cramping

Patient describes involuntary movement in the lower leg with cramping or jerking in the calves, particularly at night or while driving.

fatigue

May be related to MS primarily, but often worsened dramatically by multifactorial causes such as poor sleep hygiene, depression, restless legs, urinary frequency, or underlying sleep apnea.

urinary frequency

Multifactorial causes including damage to the central nervous system resulting in urinary retention and detrusor instability.

Urinary tract infections are more frequent in patients with urinary retention.

bowel dysfunction

Constipation is commonly seen in MS.

Bowel urgency and incontinence are almost always symptoms of constipation and should be managed as such.

spasticity/increased muscle tone

Damage to the central nervous system may result in increased muscle tone. Commonly affects the legs and can be very unpleasant and painful, disturbing sleep as well as ambulation.

increased deep tendon reflexes

Particularly clonus at the ankles and often asymmetrical.

imbalance/incoordination

Wide-based gait and/or limb ataxia indicate cerebellar dysfunction, which occurs frequently in MS.

uncommon

pale optic disk or noncorrectable visual loss

Suggestive of optic neuritis.

incorrect responses to Ishihara color blindness test plates

Damage to optic nerve may be accompanied by decrease in ability to see reds, which are seen as less intense or orange.

abnormal eye movements

Internuclear ophthalmoplegia (nystagmus of the abducting eye with absent adduction of the other eye) or isolated nystagmus may be present.

Risk factors

strong

female sex

Long described, but poorly understood, risk factor felt to be related to hormonal influences on autoimmunity, as well as on differences in recognition of self/non-self.

family history of MS

First-degree family members of patients with MS are 20-40 times more likely to develop MS than the general population.[17][18]

The age-adjusted lifetime risk for children who have one parent with MS is about 2% to 3%.[19]

The worldwide prevalence of familial MS has been estimated to be 12.6%.[20]

northern latitude

Described in epidemiologic studies and variously ascribed to genetic, environmental, and viral causes, including vitamin D deficiency related to inadequate sunlight exposure.[10][24]

weak

genetic factors

Multiple genes are felt to contribute.[22] While the HLA region is known to be a major factor in genetic susceptibility, the primary gene within the complex has not been identified and remains under study.

The interleukin receptor genes IL7 receptor alpha (IL7RA) and IL2 receptor alpha (IL2RA) have been found to be associated with increased risk of MS. These candidate genes relate to the immune system, as well as recognition of self/non-self.[21]

smoking

Cigarette smoking is associated with both increased risk for the development of MS and increased disability in people with MS.[31][32]

vitamin D deficiency

Increasing evidence suggests that low childhood sunlight exposure as well as low vitamin D levels at diagnosis are risk factors for MS.[24] There is evidence for the role of vitamin D metabolism as part of normal immune function and its disturbance in other autoimmune diseases.[33]

autoimmune disease

Patients with MS often have family members with autoimmune diseases and are more prone to developing autoimmune diseases themselves.[34]

Epstein-Barr virus

Epstein-Barr virus is the virus with the greatest link to increased risk of MS.[25][26]

overweight/obesity in children and adolescents

There appears to be a link between overweight/obesity in children and adolescents and the later occurrence of MS, particularly for girls.[35]

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