Multiple Sclerosis Clinical Presentation

Updated: Jan 03, 2023
  • Author: Christopher Luzzio, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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Attacks or exacerbations of multiple sclerosis (MS) are characterized by symptoms that reflect central nervous system (CNS) involvement. The sine qua non of MS is that symptomatic episodes are “separated in time and space”—that is, episodes occur months or years apart and affect different anatomic locations. As an example, a patient may present with paresthesias of a hand that resolve, followed a few months later by weakness in a leg or visual disturbances (eg, diplopia). In addition, the duration of the attack should be longer than 24 hours.

Presentation of MS often varies among patients. Some patients have a predominance of cognitive changes, while others present with prominent ataxia, hemiparesis or paraparesis, depression, or visual symptoms. Additionally, it is important to recognize that the progression of physical and cognitive disability in MS may occur in the absence of clinical exacerbations.

Classic MS symptoms are as follows:

  • Sensory loss (ie, paresthesias) - Usually an early complaint

  • Spinal cord symptoms (motor) - Muscle cramping secondary to spasticity

  • Spinal cord symptoms (autonomic) - Bladder, bowel, and sexual dysfunction

  • Cerebellar symptoms - Charcot triad of dysarthria (scanning speech), nystagmus, and intention tremor

  • Optic neuritis

  • Trigeminal neuralgia - Bilateral facial weakness or trigeminal neuralgia

  • Facial myokymia (irregular twitching of the facial muscles) - May also be a presenting symptom

  • Eye symptoms - Including diplopia on lateral gaze; these occur in 33% of patients

  • Heat intolerance

  • Constitutional symptoms - especially fatigue (which occurs in 70% of cases) and dizziness; fatigue must be differentiated from depression (which may, however, coexist), lack of sleep, and exertional exhaustion due to disability

  • Pain - Occurs in 30–50% of patients at some point in their illness

  • Subjective cognitive difficulties - With regard to attention span, concentration, memory, and judgment

  • Depression - A common symptom

  • Euphoria - Less common than depression

  • Bipolar disorder or frank dementia - May appear late in the disease course but is sometimes found at the time of initial diagnosis.

  • Symptoms associated with partial acute transverse myelitis

Patients with MS may present with many other manifestations, including the following:

  • Aphasia or dysphasia (occurs very rarely)

  • Seizures (5% of patients with MS)

  • Other paroxysmal symptoms (eg, ataxia, akinesia, paresthesias, pruritus)

  • Significant motor complaints without sensory deficits or dysautonomia

Paroxysmal symptoms may occur in bouts and are often triggered by movement or sensory stimuli.

Optic neuritis

Optic neuritis (ON) can be the first demyelinating event in approximately 20% of patients with MS. ON develops in approximately 40% of MS patients during the course of their disease. [57]

ON is characterized by loss of vision (or loss of color vision) in the affected eye and pain on movement of the eye. Much less commonly, patients with ON may describe phosphenes (transient flashes of light or black squares) lasting from hours to months. Phosphenes may occur before or during an ON event or even several months following recovery.

Acute transverse myelitis

Partial, rather than total, acute transverse myelitis usually is a manifestation of MS. Acute partial loss of motor, sensory, autonomic, reflex, and sphincter function below the level of the lesion indicates acute transverse myelitis. One should strongly consider mechanical compression of the spinal cord in the differential diagnosis of transverse myelitis.


Fatigue is one of the most common symptom of MS, reported by at least 75% of patients with the disease. [58] Fatigue is described as an overwhelming feeling of lassitude or lack of physical or mental energy that interferes with activities.

An estimated 50–60% of persons with MS describe fatigue as one of their most bothersome symptoms, and it is a major reason for unemployment among MS patients. One should rule out comorbid medical conditions, such as infections, anemia, vitamin deficiencies (eg, vitamin B12, folic acid, vitamin D deficiency) or thyroid disease, before attributing fatigue to MS.


Spasticity in MS is characterized by increased muscle tone and resistance to movement; it occurs most frequently in muscles that function to maintain upright posture. The muscle stiffness greatly increases the energy expended to perform activities of daily living (ADLs), which in turn contributes to fatigue.

Cognitive dysfunction

The estimated prevalence of cognitive dysfunction in MS ranges from 40–70%. No correlation exists with the degree of physical disability, and cognitive dysfunction may occur early in the course of disease. This complication of MS can be a significant problem, affecting family and social relationships, as well as employment. Areas of cognition affected may include any of the following:

  • Comprehension and use of speech

  • Attention

  • Memory

  • Visual perception

  • Planning

  • Problem solving

  • Executive function (ability to correctly follow sequential steps)

  • Abstract reasoning


As previously mentioned, pain can be a common occurrence in MS, with 30–50% of patients experiencing it at some time in the course of their illness. Pain typically is not associated with a less favorable prognosis, nor does it necessarily impair function; however, since it can have significant impact on quality of life, it needs to be treated appropriately.

Pain in MS can be classified as primary or secondary. Primary pain is related to the demyelinating process itself. This neuropathic pain is often characterized as having a burning, gnawing, or shooting quality. Secondary pain in MS is primarily musculoskeletal in nature and possibly results from poor posture, poor balance, or abnormal use of muscles or joints as a result of spasticity.

Urinary symptoms

Urinary symptoms are common in MS, with most patients experiencing problems at some point in their disease. Bladder problems are a source of significant morbidity, affecting the person's family, social, and work responsibilities. Bladder dysfunction can be classified as failure to store, failure to empty, or both. Patients with impaired storage have a small, spastic bladder with hypercontractility of the detrusor muscle. Symptoms experienced may include urgency, frequency, incontinence, and nocturia. MS patients with advancing disability and impaired bladder function may experience recurrent urinary tract infections.


Constipation is the most frequent bowel complaint in patients with MS and is characterized as the infrequent or difficult passage of stools. Constipation may be the result of a neurogenic bowel or of immobility, which leads to slowed bowel activity. In addition, patients who have limited their fluid intake in an attempt to manage bladder symptoms and those with limited access to fluids due to immobility tend to have dry hard stools.

Heat intolerance

Persons with MS often experience an increase in symptoms of fatigue or weakness when exposed to high temperatures due to weather (especially hot, humid weather), exercise, hot showers or baths, or fever. Overheating, or heat intolerance, may result in blurring of vision (Uhthoff sign), usually in an eye previously affected by ON. These symptoms result from elevation of core body temperature, which further impairs conduction by demyelinated nerves, and they typically reverse rapidly when exposure to high temperature ends.


Physical Examination

A thorough physical examination, including neurologic assessment, is critical to determine deficits in MS. All systems must be addressed, including cognition, mood, motor, sensory, and musculoskeletal, as well as the following:

  • Reflexes

  • Coordination

  • Bulbar function

  • Vision

  • Gait

  • Skin

Bulbar involvement typically refers to dysfunction of lower cranial nerves whose nuclei reside in the lower brainstem. Manifestations include dysphagia, which does not occur often in early MS and so may be attributed to a different disorder.

Patients with MS may demonstrate a variety of abnormal physical findings, and these findings may change from examination to examination, depending on the pattern of disease and whether the patient is having an exacerbation or relapse. Findings may include the following:

  • Localized weakness

  • Focal sensory disturbances (with persistent decrease of proprioception and vibration)

  • Hyperreactive reflexes with clonus in the ankles and upgoing toes

  • Increased tone or stiffness in the extremities, with velocity-dependent passive range of motion

Additional signs may include poor coordination of upper and lower extremity movements, the Lhermitte sign, and wide-based gait with inability to tandem walk.

Secondary problems may include infections, urinary problems, skin breakdown, and musculoskeletal complaints. The skin should be examined in all nonambulatory patients, and the musculoskeletal system must be addressed as appropriate.

Ophthalmologic examination

Optic neuritis, which involves the afferent visual pathway, typically causes acute to subacute unilateral loss of visual acuity, deficits in color and contrast sensitivity, visual field changes, and pain. Onset of ON typically occurs over minutes or hours, rarely days; however, loss of visual acuity may progress over days to weeks.

The loss of visual acuity in patients with ON may range from minimal to profound. In the Optic Neuritis Treatment Trial (ONTT), 35% of patients had visual acuities of 20/40 or better on entry, 30% of patients had visual acuities of between 20/50 and 20/200, and 35% of patients had visual acuities of 20/200 or worse. [59] Only 3% of patients had no light perception (NLP). Given the rarity of NLP in ON, other potential etiologies for vision loss (eg, inflammatory, infiltrative, neoplastic) need to be considered in such patients.

Most cases of ON are retrobulbar. In these cases, "the patient sees nothing, and the doctor sees nothing" (ie, the fundus is normal). The disc may show mild hyperemia, however. Severe disc edema, marked hemorrhages, or exudate should prompt reconsideration of a diagnosis of demyelinating ON.

Optic disc pallor (involving a sector or being diffuse) often occurs months after anterior or posterior ON. Uncommon fundus findings include the following:

  • Anterior uveitis

  • Vitreitis

  • Vascular sheathing

  • Disc and papillary hemorrhages

  • Compromise of the central arterial and venous circulations

The appearance of the disc does not correlate directly with the amount of inflammation, changes in visual field, or loss of visual acuity.

Patients with ON typically have loss of visual acuity in the ipsilateral eye. Contralateral and often asymptomatic visual field loss may also be detected. A relative afferent pupillary defect is present in unilateral cases and in bilateral-but-asymmetrical cases but may be absent in bilateral and symmetrical cases.

In the ONTT, nearly 100% of patients whose visual acuities were 20/50 or worse had a defect in their color sensitivity, and in those patients with visual acuities of 20/20 or better, 51–70% had altered color vision. [59] Although visual acuity typically recovers after ON, patients may continue to complain of residual deficits in color, contrast sensitivity, brightness, and stereovision.

Patients with ON may describe phosphenes (transient flashes of light or black squares) lasting from hours to months. Movement or sound may induce them. Phosphenes may occur before or during an ON event or even several months following recovery.

Visual field changes (loss of visual field is usually in the ipsilateral eye) are common in patients with ON and typically reflect nerve fiber layer defects. The classic visual field defect of ON is the central scotoma, but any nerve fiber–type defect may occur.

Most patients with ON develop retrobulbar pain that becomes worse with extraocular movement. In the ONTT, mild to severe pain was present in 92.2% of patients. [59] Pain was constant in 7.3% of patients, was constant and worse upon extraocular motility in 51.3% of patients, and was noted only with eye movement in 35.8% of patients.

Other reported visual changes in patients with ON include the following:

  • Flickering scotomas

  • Uhthoff phenomenon - Exacerbation of symptoms induced by exercise, a hot meal, or a hot bath

  • Pulfrich effect - Latencies between the eyes are unequal, resulting in a sense of disorientation in moving traffic

In addition to ON, visual disorders that may occur in MS include diplopia, oscillopsia, and nystagmus (all of which involve the efferent visual pathway).

Patients with MS may present with diplopia from an internuclear ophthalmoplegia (INO). In an INO, an adduction deficit of the ipsilateral eye is present, with horizontal gaze nystagmus in the contralateral abducting eye. The lesion involves the medial longitudinal fasciculus (MLF).

The finding of bilateral INO is strongly suggestive of MS. Diplopia in MS may also result from an ocular motor cranial neuropathy, with a sixth nerve palsy representing the most common manifestation. Third and fourth cranial neuropathies are uncommon in MS. [57] Combinations of deficits that may occur in MS include the following:

  • Horizontal or vertical gaze palsies

  • Wall-eyed bilateral INO (WEBINO) or wall-eyed monocular INO (WEMINO)

  • Paralytic pontine exotropia

  • The one-and-a-half syndrome (ie, unimpaired vertical gaze, ipsilateral eye fixed in horizontal gaze, and contralateral eye able to abduct in the horizontal plane only)

Oscillopsia can occur secondary to various types of nystagmus in MS. A new-onset, acquired pendular nystagmus is relatively common, but upbeat, downbeat, convergence-retraction, and other forms of nystagmus may also develop in MS, depending on the location of the demyelinating lesion.


Clinical Rating Scales

A patient may be rated according to several clinical disability scales, on the basis of findings on the history and physical examination. The most widely accepted of these is the 10-point Kurtzke Expanded Disability Status Scale (EDSS), which was developed originally in 1955 as the Disability Status Scale and has been revised over the years. [60]

The EDSS assigns a severity score to the patient's clinical status that ranges from 0–10 in increments of 0.5. The scores from grades 0–4 are determined using functional systems (FS) scales that evaluate dysfunction in the following 8 neurologic systems:

  • Pyramidal

  • Cerebellar

  • Brainstem

  • Sensory

  • Bladder and bowel

  • Vision

  • Cerebral

  • Other

EDSS grades are as follows:

  • 0 - Normal neurologic examination (all grade 0 in FS, cerebral grade 1 acceptable)

  • 1.0 - No disability, minimal signs in 1 FS (ie, grade 1 excluding cerebral grade 1)

  • 1.5 - No disability, minimal signs in more than 1 FS (more than 1 grade 1 excluding cerebral grade 1)

  • 2.0 - Minimal disability in 1 FS (1 FS grade 2, others 0 or 1)

  • 2.5 - Minimal disability in 2 FS (2 FS grade 2, others 0 or 1)

  • 3.0 - Moderate disability in 1 FS (1 FS grade 3, others 0 or 1) or mild disability in 3 or 4 FS (3/4 FS grade 2, others 0 or 1) though fully ambulatory

  • 3.5 - Fully ambulatory but with moderate disability in 1 FS (1 grade 3) and 1 or 2 FS grade 2, or 2 FS grade 3, or 5 FS grade 2 (others 0 or 1)

  • 4.0 - Fully ambulatory without aid; self-sufficient; up and about some 12 hours a day despite relatively severe disability, consisting of 1 FS grade 4 (others 0 or 1) or combinations of lesser grades exceeding limits of previous steps; able to walk approximately 500 m without aid or resting

  • 4.5 - Fully ambulatory without aid; up and about much of the day; able to work a full day; may otherwise have some limitation of full activity or require minimal assistance; characterized by relatively severe disability, usually consisting of 1 FS grade 4 (others 0 or 1) or combinations of lesser grades exceeding limits of previous steps; able to walk approximately 300 m without aid or rest

  • 5.0 - Ambulatory without aid or rest for approximately 200 m; disability severe enough to impair full daily activities (eg, to work full day without special provisions; usual FS equivalents are 1 grade 5 alone, others 0 or 1; or combinations of lesser grades usually exceeding specifications for step 4.0)

  • 5.5 - Ambulatory without aid or rest for approximately 100 m; disability severe enough to preclude full daily activities (usual FS equivalents are 1 grade 5 alone; others 0 or 1; or combinations of lesser grades usually exceeding those for step 4.0)

  • 6.0 - Intermittent or unilateral constant assistance (cane, crutch, or brace) required to walk approximately 100 m with or without resting (usual FS equivalents are combinations with more than 2 FS grade 3+)

  • 6.5 - Constant bilateral assistance (canes, crutches, or braces) required to walk approximately 20 m without resting (usual FS equivalents are combinations with more than 2 FS grade 3+)

  • 7.0 - Unable to walk beyond approximately 5 m even with aid; essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about approximately 12 hr/day (usual FS equivalents are combinations with more than 1 FS grade 4+; very rarely, pyramidal grade 5 alone)

  • 7.5 - Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair (usual FS equivalents are combinations with more than 1 FS grade 4+)

  • 8.0 - Essentially restricted to bed or chair or perambulated in wheelchair but may be out of bed itself much of the day, retains many self-care functions; generally has effective use of arms (usual FS equivalents are combinations, generally grade 4+ in several systems)

  • 8.5 - Essentially restricted to bed much of the day; has some effective use of arms; retains some self-care functions (usual FS equivalents are combinations, generally 4+ in several systems)

  • 9.0 - Helpless bedridden patient; can communicate and eat (usual FS equivalents are combinations, mostly grade 4+)

  • 9.5 - Totally helpless bedridden patient; unable to communicate effectively or eat/swallow (usual FS equivalents are combinations, almost all grade 4+)

  • 10.0 - Death due to MS

Advantages of the EDSS are that it is widely used clinically, is easy to administer, and requires no special equipment. Its limitations are as follows:

  • It is heavily dependent on mobility

  • It is somewhat subjective in certain areas (eg, bowel and bladder function)

  • It is insensitive to small changes

  • It does not present an accurate picture of the patient's cognitive abilities and functional abilities in performing activities of daily living (ADLs)

  • It is nonlinear in terms of the time spent at various ranges of the scale

Despite its limitations, the EDSS is often used as a standardization measure for clinical trials.

Other useful scales include the Ambulation Index, which is based solely on the ability to walk 25 feet, and the Multiple Sclerosis Functional Composite (MSFC), which includes the Ambulation Index, the 9-hole peg test, and the PASAT attention test. The MSFC is reported as z scores, which have been difficult to translate into clinical significance. In addition, the Scripps Neurologic Rating Scale, developed by Sipe in 1984, has been used by some investigators. This scale has a finer incremental scale than the Kurtzke scale, but it is not widely accepted and does not consider cognitive involvement.


Criteria for Categorizing MS

MS is divided into the following categories, principally on the basis of clinical criteria, including the frequency of clinical relapses, time to disease progression, and lesion development on MRI: [61, 2, 3, 4]

  • Relapsing-remitting MS (RRMS)

  • Secondary progressive MS (SPMS)

  • Primary progressive MS (PPMS)

  • Progressive-relapsing MS (PRMS)

RRMS is characterized by recurrent attacks in which neurologic deficits appear in different parts of the nervous system and resolve completely or almost completely over a short period of time, leaving little residual deficit. Patients with a relapsing-remitting pattern account for approximately 85% of MS cases (see the images below).

MRI of the head of a 35-year-old man with relapsin MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. MRI reveals multiple lesions with high T2 signal intensity and one large white matter lesion. These demyelinating lesions may sometimes mimic brain tumors because of the associated edema and inflammation.
MRI of the head of a 35-year-old man with relapsin MRI of the head of a 35-year-old man with relapsing-remitting multiple sclerosis. This MRI, performed 3 months after the one in the related image, shows a dramatic decrease in the size of lesions.

Two subgroups sometimes included in RRMS are clinically isolated syndrome (CIS) and benign MS. CIS consists of a single episode of neurologic symptoms; it is sometimes labeled possible MS. In benign MS, patients have almost complete remission between relapses, and even 15–20 years after diagnosis they have little if any accumulation of physical disability. Making a diagnosis of benign MS too early during the course of the disease is discouraged, since MS can worsen, sometimes drastically, in patients with a history of mild manifestations at onset.

Global clinical deterioration in RRMS has traditionally been attributed to cumulative deficit due to incomplete recovery from repeated occurrences of individual relapses. However, evidence increasingly suggests an ongoing background neurologic deterioration that is independent of relapses.

Although MS was previously thought to be silent between relapses, magnetic resonance imaging (MRI) studies have demonstrated that inflammatory events are occurring in the brain at 10–20 times the predicted rate indicated by the mean relapse rate. This silent disease activity can occur in both white and gray matter and is associated with cerebral atrophy, which in most patients is evident in volumetric studies even at diagnosis.

Natural history data indicate that approximately 50% of patients with RRMS convert to a secondary progressive pattern within 10–15 years after disease onset. This pattern may or may not include relapses, but it is characterized by continued progression over years, with increasing disability. Treatment with disease-modifying agents is thought to slow the progression of RRMS. Unlike RRMS, SPMS without relapses does not seem to be responsive to currently available disease-modifying agents. [62]

In PPMS, which accounts for approximately 10% of MS cases, function declines steadily without relapses. In PRMS, which accounts for fewer than 5% of patients with MS, occasional relapses are superimposed on progressive disease.