Multiple Sclerosis

PHYT 7427
Neurological PT
Diagnosis & Management II

O’Sullivan Ch. 16 (2014)

Umphred Ch. 19 (2013)
[Lundy-Ekman pg 20, 24, 41-43, 321]

by
Jacob F. Brewer, PT, DPT, Ph.D., NCS
 Multiple Sclerosis (MS):
a chronic, progressive, inflammatory
disorder of the central nervous system

MS is an unpredictable and progressively disabling disease. Patients

with MS typically are diagnosed at a young age, and they face
decades of uncertainty, with progressively declining health, ever
increasing lifestyle limitations and reduced quality of life.
 General Information
• Major cause of disability in young adults
• Hallmark of disease process:
– Sclerotic plaques throughout CNS
• Lesions slow or block neural transmission
• Resulting in:
– Weakness
– Sensory loss
– Visual dysfunction
Prevalence of Neurological Conditions (per 100,000 in 1 Yr)
 Epidemiology
- 2.1 million cases worldwide
- Higher prevalence in those with northern
European ancestry
- Higher incidence in women (3:1)
Ratio has been increasing
- Typical age of onset 20-50 years
- 2–5% have symptom onset before age 18
- 85% have relapsing/remitting disease course
 
The National Multiple Sclerosis Society. www.nationalmssociety.org Accessed December 2012.
 - Approximately 400,000 cases in the US

- Up to 10,000 new cases per year

~ 200 per week
- Most common neurological disease in
  young adults - usually diagnosed in 20’s-30’s

The National Multiple Sclerosis Society. www.nationalmssociety.org

 Etiology
• “An autoimmune process that occurs in a genetically susceptible
person after an environmental exposure”

• Myelin damage most likely due to immune system

• Possible environmental factor

• Viral infection can precipitate attacks

• Vaccinations may be associated with increasing attacks

• Clear genetic component

 Recurrence risks for multiple sclerosis

Genetic
sharing Relationship

MZ twin
14
100%
Sibling, 2 aff.parents
13
Sibling, 1 aff. parent
12
11
10
DZ twin
50%
9
Sibling

Parent
8
7
Child

Half sibling

25%
6
Aunt / uncle
5
Nephew / niece
4
12.5% Cousin
3
0%
Adoptee
2
General population
1
0
0 5 10 15 20 25 30 35
Lifetime risk (%)
 Etiology?

Linkage — Multiple Sclerosis and Ionizing Radiation. By Walter B. Eidbo, M.D. & Merle P. Prater, Ph.D
2004 International Radon Symposium
 Genetic Factors

Autoimmune

Disease

Immune Environmental
Regulation Factors
Smoking, Vitamin D deficiency
Lack of sun exposure , EBV,
Neuro-excitotoxins, etc.
 Pathogenesis
• Demyelinating disorder of CNS damaging:
– Myelin sheath and axons

• Gross yet significant atrophy in cerebral hemispheres

– Numerous small, irregular gray areas in white matter

• Changes may occur in spinal cord

• Microscopically, plaques throughout cerebral hemispheres

– Periventricular region
– Corpus callosum
– Optic nerves
– Brain stem
Pathology of MS
Figure 02-03   Myelination. A, Oligodendrocytes provide myelin sheaths in the central nervous
system. B and C, Schwann cells provide insulation to peripheral nerves. Myelinated axons are
completely enveloped by Schwann cells. Unmyelinated axons are partially surrounded.
• Immune system T cells normally in the bloodstream become activated
against components of the brain myelin.
• They cause local inflammation in scattered regions of the brain and spinal
cord once they cross the barrier between the bloodstream and CNS.
The destruction of the myelin sheath leads to
impaired communication between nerve cells
and neurological symptoms such as abnormal
sensations, vision problems, and weakness.
This can result in damage and lost fibers.
Nerves can sometomes regain myelin, but process is not
fast enough to avoid the deterioration that occurs in MS
Astrocytes form scars where myelin formerly existed
Inflammation, loss of myelin, and nerve fibers, and the
following scarring result in reduced transmission of nerve
signals within the CNS.
Types of symptoms and severity vary widely due to the
location of the scar tissue and extent of demyelination
 • An immune-mediated disease in genetically susceptible
individuals

• Demyelination leads to slower nerve conduction and/or

conduction block at the site of lesion

• Axonal injury and destruction are associated with permanent

neurological dysfunction

• Lesions occur in optic nerves, periventricular white matter,

cerebral cortex, brain stem, cerebellum, and spinal cord

Trapp BD et al. N Engl J Med. 1998;338:278-285.

 …and related symptoms vary widely in
incidence and severity

Cognitive loss

Emotional disinhibition

Tremor, Optic neuritis

Ataxia
Diplopia
Vertigo
Dysarthria
Sensory symptoms,
INO
Lhermitte’s SIgn
Pain
Proprioception Bladder dysfunction
 Clinical Presentation of MS
SENSORY TRACTS
- Numbness & tingling -paresthesia/ dysthesia.
- Often begins in the distal limbs and migrates proximally.

CORTICOSPINAL TRACTS
- Heaviness, weakness, hyperreflexia, positive Babinski,
mild spasticity

BRAINSTEM
Eye movement abnormalities: diplopia, nystagmus

VISUAL PATHWAY
Optic neuritis - frequent presenting symptom
 Clinical Presentation of MS (con’t)
CEREBELLER
- Gait ataxia, limb ataxia , tremor, coordination & balance problems

FRONTAL LOBE
- Cognitive dysfunction and/or emotional dysinhibition, depression, anxiety

TEMPORAL LOBE
- Aphasia

CORPUS CALLOSUM
- Cognitive Dysfunction

FATIGUE
- Presents in up to 90% of patients, common but nonspecific

ELIMINATION: (Brainstem / spinal cord)

- Bladder urgency, frequency, hesitation, nocturia
- Bowel constipation, infrequency & involuntary movements
Miller A. Clinical features. In: Cook S.ed. Handbook of Multiple Sclerosis, 3rd edition. New York: Marcel Dekker; 2001:213-224
Paty D. Initial Symptoms. In: Burks J.JohnsonK, eds.Multiple Sclerosis Diagnosis, Medical Management & Rehabilitation. NY Demos: 2000
Medical Management
 Diagnosis
• Clinical judgment and observation over time

• MRI is the single most useful test in confirming MS and is abnormal in 90% of
suspected cases

• CSF analysis:
– Increased mononuclear cell pleocytosis
– Elevated total immunoglobulin
– Presence of oligoclonal bands

• Evoked potential response show slowed or abnormal conduction in these

pathways:
– Visual
– Auditory
– Somatosensory
– Motor
 Diagnosis of MS

CSF (Cerebrospinal fluid)

 Fluid examined for
cells, proteins, and
electrolytes
 Proteins examined for
presence of oligoclona.
 NOT COMMON IN
EARLY CASES
 Diagnosis:
“Possible” vs. “Definite” MS
General Physical
History of all complaints of
patients general health
MRI (Magnetic Resonance
Imaging)
Detects patchy areas of
change in the CNS
• MRI FLAIR sequence showing four bright
spots (plaques) where multiple sclerosis has
damaged myelin in the brain
• Multiple Sclerosis: T1-weighted MRI (post-
contrast) of same brain slice at monthly intervals.
• Bright spots indicate active lesions.
• Source U.S. Brookhaven National Laboratory: Quantitation of Blood-Brain Barrier Permeability in MS Lesion
Multiple sclerosis: lesion sites and syndromes

Cerebral lesions – usually clinically silent

….. brain stem - impaired co-ordination

of eye movements, speech, limbs and
balance

…. optic nerve – pain on movement and

reduced vision in one eye

…. spinal cord – small and multiple

summating to disorders of movement,
sensation and sphincter control
Disease Course and Clinical
Patterns
 Clinical Manifestations
• Symptoms may develop quickly over a few hours or over
several days or weeks

• Initial symptoms may be transient and not even reported

• Sensory changes most often the initial complaint:

– Paresthesia or dysesthesia in head and face
– Visual blurring
– Diplopia
– Weakness
– Balance problems
Clinical Manifestations (cont’d)
• Optic neuritis is often the first event in MS

• 50% to 70% have some cognitive involvement

• Average number of attacks per year is 1

• Characterized by progressive disability over time but is variant

per individual

• Capacity of the individual’s brain to adapt to the lesions will

determine the severity of clinical manifestations
(neuroplasticity)
 Clinical Patterns
• Clinical course divided into categories according to
neurologic symptoms as they develop over time

• Categories:
– Relapsing-remitting (RR-MS)
– Secondary-progressive (SP-MS)
– Primary-progressive (PP-MS)
– Progressive-relapsing (PR-MS)
 Relapsing-Remitting (RR-MS)
• Most common pattern in those younger than 40

• Relapses or attacks lasting days to months followed by full or

partial recovery

• New symptoms lasting 24 hours and separated from other

symptoms by at least 30 days to qualify as a new attack

• There is a stable course between relapses

• Most eventually convert to SP-MS

 Secondary-Progressive (SP-MS)
• Initial pattern of RR-MS that progressively worsens over months (at
least 6) to years

• Conversion generally occurs 10 to 20 years after initial onset of

relapsing symptoms or after 40

• The clinical course becomes a steadily progressive pattern over time

• May continue to have relapses during this phase but does not stabilize
between relapses

• Over time, relapses become less discrete, and the pattern becomes one
of continued worsening without relapses
 Primary-Progressive (PP-MS)
• Accounts for 10% to 15% of cases

• Most likely male older than 40 years at time of onset

• Characterized by progressive worsening from the onset of symptoms

without interposed relapses

• There is a steady decline in neurologic function from the outset with

episodes of minimal recovery

• Often presents with progressive gait disorder as a result of leg

weakness, spasticity, and impaired coordination
 Progressive-Relapsing (PR-MS)
• Progressive disease from the onset with one or
more relapses

• May be another form of SP-MS without

clinically apparent relapses in the early stages
of the disease

• Rarest form of MS, only about 6% of cases

 Relapsing-remitting Secondary-progressive
Disability

Disability
Time Time
Primary-progressive Progressive-relapsing
Disability

Disability

Time Time
Lublin FD, Reingold SC. Neurology. 1996;46:907-911.
 Natural History Over Time

Relapsing-remitting Secondary-progressive
Primary-progressive Relapsing-remitting

15% 42%

85% 58%

Disease Type at Diagnosis Disease Type at 11-15 Years

After Diagnosis (Among Those
With RRMS at Diagnosis)

Adapted from Weinshenker BG et al. Brain. 1989;112:133-146.

15 Years After Diagnosis

-- 20% of MS patients have no functional

limitation

-- 70% are limited or unable to perform major

activities of daily living

-- Most individuals become unemployed

 Presentation of Syndromes
• Corticospinal Syndrome:
– Corticospinal tract involvement
– Dorsal column symptoms
• Brain Stem Syndrome
• Cerebellar Syndrome
• Cerebral Syndrome
 Corticospinal Syndrome
• Most common, involving corticospinal tracts
and dorsal column
• Bladder and bowel symptoms especially with
spinal cord involvement
• Residual urine after emptying with subsequent
overflow incontinence
• Heightened risk of UTI
Corticospinal Syndrome (cont’d)
• Corticospinal tracts involvement:
– Stiffness, slowness, and weakness
– Spasticity in 90% of cases
– Associated UMN signs may include clonus,
spontaneous extensor or flexor spasms, positive
Babinski’s sign, loss of precise autonomic control
– Muscle activation patterns and agonist-antagonist
relationships are disturbed
Corticospinal Syndrome (cont’d)
• Dorsal column symptoms:
– Paresthesias (tingling, prickling)
– Hypoestheisa (diminished sensitivity)
– Feeling of swelling, wetness, or body part being
tightly wrapped
– Loss of vibration, position, and 2-point
discrimination
 Brain Stem Syndrome
• Lesions of cranial nerves III through XII at the root,
nuclear, or bulbar level
• Gaze palsies – loss of active control of eye movement
• Nystagmus – involuntary rhythmic tremor of the eye
• Dysarthria – abnormal speech resulting from poor
control of the muscles of speech
• Vertigo, unsteady gait and vomiting may occur
• Spasm or weakness of facial muscles
 Cerebellar Syndrome
• Can be symmetric involving all limbs or
asymmetric involving only one side
• Ataxia, hypotonia, truncal weakness causing
postural and movement disorders
• Dysarthria of cerebellar origin
• Often associated with progressive phases of the
illness
 Cerebral Syndromes
• Optic neuritis – unilateral, painful decrease or
loss of vision
• Depression and progressive cognitive
dysfunction
• Emotional lability and emotional incontinence
• Memory loss
 Other Symptoms
• Lhermitte’s sign – a momentary electric-like
sensation evoked by neck flexion or cough
• Neurogenic burning pain in thorax or legs
• Heat sensitivity
• Fatigue
• Back pain
 Other Variants and Mimickers
• Marburg Disease
– Acute rapidly progressive form of MS
– Leads to severe disability within days or months
• Neuromyelitis optica
– Presents with both optic neuritis & transverse myelitis
– Most likely older female at time of onset
• Acute disseminated encephalomyelitis
– Thought to be forms of immune-mediated inflammatory
demyelination
– Present with fever, HA, meningeal signs, altered consciousness
– Differ from MS in that they are typically monophasic
• MS is multiphasic or chronically progressive
 Common Signs and Symptoms
• Visual blurring • Band like disturbance
• Vision loss/eye pain • Falls
• Diplopia • Lack of coordination
• Oscillopsia • Inability to concentrate or learn
• Loss of dexterity • Easily distractible
• Weakness • Emotional lability
• Tightness & pain • Depression
• Shaking • Fatigue
• Imbalance • Pain
• Paresthesias • Urinary urgency, hesitancy,
• Loss of sensation frequency, & incontinence
 Medical Treatment
• Disease-modifying therapies
– Interferon may alter the course of disease
• Evidence indicates should be started early in course of the
disease

• Combination therapies

• Symptomatic therapies
• Acute attacks with high dose steroids and immunotherapy
• Corticosteroids and ACTH can shorten recovery period
after acute attack
 Interferons

 Discovered in 1957

 Significant antiviral agents

 phenomenon where one

infection with one virus
interferes with a
subsequent infection with
another virus
 Interferons: What are they?
•A protein substance naturally produced in the
body and believed to function to modulate the
immune system.

•Interferons interact with receptors on non-

infected cells to promote the synthesis of
antiviral proteins that prevent further infection.

•They belong to Cytokines, which are hormones

of the immune system.
 Beta Interferon
Beta interferon-1a
 Avonex – administered weekly by an
intramuscularly injection (2003)
 Rebif – administered subcutaneously
three times a week (2002)

Beta interferon-1b
 Betaseron – administered
subcutaneously every other day (1993)
 Prognosis

• Modest reduction in life expectancy

• Disability forces lifestyle changes

• Death associated with severe disability

 When to Refer
• Symptoms that are suspicious for MS include:
– Unexplained numbness/tingling
– Fatigue
– Urinary urgency
– Loss of vision in one eye
– Impaired coordination
 Rehabilitation
• Directed Toward:
– Maximizing function
– Preventing unnecessary complications
– Empowering individuals
– Reducing disablement

• Evaluation:
– Development of patient profile
 MS Outcome Measures
Multiple Sclerosis
Quality of Life Index (MSQLI)

• Health Status Questionnaire (SF-36) - 36 items

• Modified Fatigue Impact Scale (MFIS) - 21 items*
• MOS Pain Effects Scale (PES) - 6 items
• Sexual Satisfaction Scale (SSS) - 5 items
• Bladder Control Scale (BLCS) - 4 items
• Bowel Control Scale (BWCS) - 5 items
• Impact of Visual Impairment Scale (IVIS) - 5 items
• Perceived Deficits Questionnaire (PDQ) - 20 items*
• Mental Health Inventory (MHI) - 18 items*
• MOS Modified Social Support Survey (MSSS) - 18 items*
*(Abbreviated 5 item versions of these scales are also available)
www.nationalmssociety.org
 MS Outcome Measures

• Expanded Disability Status Scale (EDSS)

• MS Quality of Life Inventory (MSQLI)
• MS Spasticity Scale (MSSS-88)
Expanded Disability Status Scale (EDSS)
The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in
multiple sclerosis. The EDSS replaced the previous Disability Status Scales which used to bunch
people with MS in the lower brackets.

The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a
Functional System Score (FSS) in each of these.

The Functional Systems are:

• pyramidal
• cerebellar
• brainstem
• sensory
• bowel and bladder
• visual
• cerebral
• other

EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory.

EDSS steps 5.0 to 9.5 are defined by the impairment to ambulation.

Expanded Disability Status Scale (EDSS)
 Treatment Considerations
• Fatigue (most common symptom)
• Spasticity
• Weakness
• General conditioning and fatigue
• Balance and coordination problems
• Ambulation and mobility problems
• Dizziness and vertigo
• ADLs
Treatment Considerations (cont’d)
• Pain (often neuropathic pain)
• Dysarthria and dysphagia
• Sensory dysfunction
• Cognitive impairment
• Bladder and bowel problems
• Sexual dysfunction
• Depression
 Clinical Presentation
• Muscle weakness
• Mild sensory symptoms
• Diminished or absent DTRs
• Impaired respiratory muscles
• Pain – especially lumbar
• Autonomic dysfunction
• History of flulike illness common
 Physical Therapy Issues
• Fatigue
– Energy conservation, moderate exercise, rest, assistive device, work
simplification, cooling

• Spasticity Management
– As per other conditions we have discussed

• Strengthening
– Focus more on submaximal effort to avoid fatigue issues

• Equipment
– Assistive devices, power wheelchairs, AFOs

• Balance/Vertigo

• Pain
– Treat underlying orthopedic causes
 MS & Physical Therapy
• Improvement of strength, endurance, reduction of
spasticity, prevent or slow decline of function,
promote regular exercise, good health, self
management

• Interventions – direct interventions, patient-related

instruction, environmental modifications, supportive
counseling

• Maximal exercise is not tolerated

 MS & Physical Therapy
• Aquatic Therapy – resistance training, endurance, static &
dynamic postural control, slows ataxic movements, moderate or
cool temp. (no greater than 85˚) to control spasticity

• PNF Patterns – reduce tone, combines actions of major

synergistic muscle groups, more economical for fatigued
patient, promote stability

• Functional Training – focus on problem solving skills,

compensatory strategies (strengthen unaffected ms. Groups),
assistive devices, energy conservation techniques

• Modalities – for pain management, spasticity, relaxation

 Prognosis

• Point of greatest severity

• Onset of recovery

• Long-term deficits
• Cause of death
Flexibility Exercises for MS
Flexibility Exercises for MS
Management of Coordination
and Balance Deficits in MS
Management of Coordination
and Balance Deficits in MS
Management of Coordination
and Balance Deficits in MS
Management of Coordination
and Balance Deficits in MS
Management of Coordination
and Balance Deficits in MS
Locomotor Training in MS
 Locomotor Training in MS:
Orthotics and Assistive Devices
Power-Mobility in MS
Multiple Sclerosis

PHYT 7427
Neurological PT
Diagnosis & Management II

QUESTIONS?
Jacob F. Brewer, PT, DPT, Ph.D., NCS