MULTIPLE SCLEROSIS

y Multiple sclerosis (MS) is an inflammatory,

demyelinating disease of the central nervous system (CNS).

y MS lesions, characterized by perivascular

infiltration of monocytes and lymphocytes, appear as indurated areas in pathologic specimens; hence, the term sclerosis in plaques.

y MS is a dynamic disease, with almost constant lesion

formation and a progressive clinical course leading to physical disability.

y For every 8-10 new lesions detected on magnetic

resonance imaging (MRI), only one clinical manifestation typically can be demonstrated.
y Patients with relapsing remitting MS have an average

of 5-10 new lesions per year and 1 or 2 clinical exacerbations.

ETIOLOGY
y Despite intensive efforts in finding the source of the

disease, no etiologic agent for MS has been identified.

y The disease presumably can be exacerbated by

hormonal changes during the postpartum period.

y Some argue that MS could be a heterogeneous

disorder triggered or perpetuated by several different environmental agents. In fact, only 1 of every 4 MS attacks is associated with an intercurrent infection.

DEMOGRAPHICS OF MS
y Frequency  More than 2.5 million people worldwide are estimated

to be affected by multiple sclerosis.

 Highest incidence in US and Northern Europe.  It is believed to be a disease of Caucasians (light

skinned people from Europe, North African, Western Asia and India). People living closer to equator show lesser incidence of this disease.

 MS in India has Optico-spinal phenotype (as

generally reported in Asian population). Which means that the attacks are mostly confined to optic nerve and spinal cord.
 In India alone, there are 40,000 to 50,000 people

who are affected with MS.

Mortality/Morbidity
 Multiple sclerosis causes considerable disability in the

working age group.

 People with MS usually die of complications related to

MS disability rather than of MS itself (eg, recurrent respiratory tract infections in bedridden patients due to difficulty in handling secretions).
 Patients with MS are thought to have an average life

expectancy 5-7 years shorter than that of the general population.

Race  Multiple sclerosis presents more often in populations of northern European ancestry.  Disease severity or drug treatment effect variability may be accounted for, at least in part, by racial or geographic differences. Sex  Multiple sclerosis affects females more than males (1.6-2:1), but the basis for this difference is unknown.  This ratio is even higher (3:1) among patients in whom onset of MS is before age 15 years or after age 50 years, suggesting a hormonal component to the disease process.

 Males have a greater tendency to develop primary

progressive MS, while females tend to experience more relapses. Age  Multiple sclerosis most commonly afflicts people aged 18-50 years, but any age group can be affected.

CLINICAL FINDINGS IN MS
y CAUSES

 The cause of multiple sclerosis is unknown. Multiple

factors are likely to act.

 These factors are in part environmental and in part

hereditary: 1. An environmental agent or event (eg, virus, bacteria, chemicals, lack of sun exposure) has been hypothesized to act in concert with a specific genetic predisposition (ie, a set of genes or polymorphisms) to result in immune dysfunction.

2. HLA-DRB1 is the only chromosomal locus that has been consistently associated with MS susceptibility. 3. The co-stimulatory molecule B7-1, necessary for activation of T cells as a second signal to antigen presentation, has been found to be elevated in early MS lesions, suggesting a triggering role for inflammation within the CNS. 4. Peripheral blood T cells may become activated to attack a foreign antigen, then direct their attack toward brain proteins that share similar protein.

5. Hypothesis - that a virus may infect the immune system, activating self-reactive T cells (myelin reactive) that would otherwise remain quiescent.

PATHOPHYSIOLOGY OF MS
 The mechanism of demyelination in multiple sclerosis may be

activation of myelin-reactive T cells in the periphery, which then express adhesion molecules, allowing their entry through the blood-brain barrier (BBB).
 T cells are activated following antigen presentation by antigen-

presenting cells such as macrophages and microglia, or B cells.

 Perivascular T cells can secrete proinflammatory cytokines,

including interferon gamma and tumor necrosis factor alpha.

 Antibodies against myelin also may be generated in the periphery

or intrathecally.

HISTORY
y Attacks or exacerbations of multiple sclerosis are

characterized by new symptoms that reflect CNS involvement.

y These symptoms are typically separated in time (eg, by

months or years) and in anatomical location (eg, weakness of one or more limbs, optic neuritis, sensory symptoms).
y Recognizing that physical and cognitive disability

progression in MS may occur in the absence of clinical exacerbations is important.

Staging of ms

RELAPSING REMITTING MS (RRMS)

y Patients who improve after acute attacks have

relapsing remitting MS (RRMS).

y However, during the natural course of RRMS,

approximately 75-85% of patients enter a stage referred to as secondary progressive MS (SPMS).

PRIMARY PROGRESSIVE MS (PPMS)

y Patients with primary progressive MS (PPMS) tend to

accumulate disability without interruption (ie, without remissions) from the time of disease onset.
y Some of these patients first present with weakness of only

one limb, which gradually progresses to involve other limbs and may culminate in total paralysis.
y Patients with PPMS typically respond poorly to the current

therapeutic options for MS, accumulate disability faster than other patients, and tend to have more weakness of the legs as well as incontinence (a reflection of greater spinal cord involvement).

RELAPSING PROGRESSIVE MS (RPMS)

y Patients who have RRMS but accumulate disability

between and during attacks can be defined as having relapsing progressive disease (RPMS).

y Although most patients have a wide range of

symptoms from lesions in different areas of the brain and spinal cord, others may present with predominantly visual, cognitive, or cerebellar symptoms.

BENIGN MS
y The term benign multiple sclerosis is most often applied

to cases where the disease is shown to have run a mild course over the years (approx 10% of MS cases).
y Making a diagnosis of benign MS too early during the

course of the disease is discouraged since MRI and clinical activity can worsen, sometimes drastically, in patients with a history of mild manifestations at onset.

CLINICAL FEATURES
y Patients with MS tend to experience variable degrees of fatigue. o This symptom is typically described as either physical exhaustion or

mental/cognitive slowing.
o It must be differentiated from depression (which may, however,

coexist), lack of sleep, and exertional exhaustion due to disability.

o Patients may feel particularly fatigued after taking a hot shower or

after strenuous activity in heated environments.

y Heat exposure may also lead to episodes of optic nerve dysfunction

(ie, Uhthoff phenomenon), the mechanisms of which remain poorly understood.

y MS may present in various forms, some patients have a

predominance of cognitive changes, while others present with prominent ataxia, hemiparesis or paraparesis, depression, or visual symptoms.
y Symptoms can be exacerbated by intercurrent illness,

including viral or bacterial upper respiratory or urinary tract infections.

y Trauma has no impact on disease exacerbation. y Optic neuritis presents clinically as orbital pain, at rest or

during eye movement, and loss of vision. Patients may complain of "patchy loss of vision," and upon examination

y Patients may experience color desaturation even

with normal visual acuity, usually manifested as the perception of red color as different shades of orange or grey.
y Patients with MS may present with facial palsies or

trigeminal neuralgia. In fact, the presence of bilateral facial weakness or trigeminal neuralgia strongly suggests the diagnosis of MS.
y Nystagmus (direction-changing) and

ophthalmoplegia signs are other manifestations.

y Painful limb syndromes are important to recognize, as those

with paroxysmal qualities may respond better to specific treatments.

y Patients with MS also commonly complain of numbness or

tingling in one or more limbs, variable weakness, or sensory level-related symptoms.

y An often overlooked manifestation of MS is the pseudobulbar

affect, whereby patients have difficulty controlling their emotions (laughing, crying) and are perceived to act inappropriately by coworkers or friends.
y Urinary retention and incontinence are common. Bowel

habit changes may occur, but bowel incontinence is less frequent.

y Sexual dysfunction affects the great majority of

patients with MS and includes symptoms such as lack of desire, erectile dysfunction, impaired sexual responsiveness, premature ejaculation, impaired genital sensation

DIFFERENTIAL DIAGNOSIS
y Acute disseminated encephalomyelitis y Brainstem gliomas y Hemifacial spasm y Primary lateral sclerosis y Spinal cord infarction

INVESTIGATIONS
y LAB STUDIES 1.

CSF examination Oligoclonal bands are distinct that reflect substantial elevation of IgG are demonstrated in CSF samples of approximately 85% of patients with multiple sclerosis.

  

Glucose level is usually normal. Protein level can be normal or slightly elevated. WBC count can be slightly to moderately elevated

2. Blood work
 An elevated erythrocyte sedimentation rate (ESR) and

positive titers of rheumatoid factor (RF) should help identify the presence of a vasculitic disorder that may be mimicking MS.
 Patients with optic neuritis and longitudinally

extensive spinal cord lesions by MRI should be tested for neuromyelitis optica (NMO), searching for the presence of aquaporin 4 antibodies in the serum.

y If clinical suspicion for a peripheral neuropathy arises,

electrophysiological studies and blood tests for metabolic or toxic neuropathies should be performed. 3. Imaging studies- MRI scans Typical multiple sclerosis lesions appear as T2 hyperintensities in the periventricular regions; They have an ovoid appearance with their largest axis oriented perpendicular to the ventricular surface; They typically involve only the white matter, and several arise from the corpus callosum

y Lesions that enhance with gadolinium are thought to

reflect active disease, as enhancement may correspond to breakdown of the blood-brain barrier from an ongoing subacute inflammatory process (few days to a few weeks).
y Usually a combination of enhancing and nonenhancing

lesions is seen, reflecting the chronicity of the demyelinating process.

4. Evoked potentials
 Evoked potential testing (visual, auditory, or

somatosensory).
 the most sensitive are the visual evoked potentials (50-80%

sensitivity), followed by the somatosensory potentials (5070% sensitivity). 5. Lumbar puncture Histopathologic examination reveals that multiple sclerosis lesions are caused by perivenular infiltration of lymphocytes (most of which are CD4+ T cells) and macrophages

MEDICAL MANAGEMENT
y Amantadine (Symmetrel) or Modafinil (Provigil) is

often attempted when no contraindications exist.

y Pemoline- a drug that was gaining attention by MS

clinicians for the treatment of fatigue is no longer being used due to reports of rare fatal liver damage events during its use.

y Immunomodulatory drugs

Eg. 1. Interferon beta-1a IM [Avonex] 2. Interferon beta-1b SC [Betaseron and Extavia] 3. Glatiramer acetate SC [Copaxone] 4. Interferon beta-1a SC [Rebif]
y These 5 medications have been approved by the FDA and

are currently used widely in the United States for MS.

y As a rule of thumb, these drugs tend to decrease the rate of

MS relapses by approximately one third, with the highest efficacy demonstrated in clinical trials for the high-dose, high-frequency (HDHF).

ACUTE EXACERBATIONS
 Most widely used treatment is intravenous (IV)

methylprednisolone, 1 g IV qd for 3-5 days

 High-dose IV steroids may work more effectively than

oral steroids for the acute attack, and home IV therapy is recommended if the patient does not require hospitalization.

SECONDARY PROGRESSIVE FORMS

 Patients with relapsing forms of MS who are transitioning

to SPMS may be treated with HDHF interferons if they are still experiencing relapses.
 Mitoxantrone- Patients on mitoxantrone need to be

monitored with echocardiograms prior to, during and after treatment, as the drug carries a risk of cardiomyopathy. Because of this risk, mitoxantrone is typically reserved for patients with aggressive clinical presentations of MS (ie, worsening MS) or in whom immunomodulatory drug therapy has failed.

SYMPTOMATIC MEDICATION
y Decreased walking speed - Dalfampridine

(Ampyra)
y Depression - Fluoxetine (Prozac), sertraline (Zoloft),

amitriptyline (Elavil)
y Spasticity - Baclofen, tizanidine, dantrolene,

diazepam (Valium), intrathecal baclofen delivered via programmable pump

y Painful tonic spasms - Baclofen, carbamazepine

(Tegretol), gabapentin (Neurontin), phenytoin

y Fatigue - Modafinil, amantadine, fluoxetine,

methylphenidate (Ritalin)
y Urinary dysfunction - Propantheline bromide (Pro-

Banthine), tolterodine tartrate, oxybutynin (Ditropan), imipramine (Tofranil); intermittent self-catheterization

y Tremors/ataxia - Clonazepam (Klonopin), primidone

(Mysoline), propranolol (Inderal), gabapentin; weighted bracelets

y Erectile dysfunction - Sildenafil (Viagra), tadalafil

(Cialis), vardenafil (Levitra), alprostadil (Muse)

SUGICAL MANAGEMENT
y Surgical procedures that relate to multiple sclerosis are

directed primarily at alleviating symptoms :

 Dysphagia - gastrojejunal tube placement  Significant limb spasticity or contractures -

Adductor leg muscle tendon release, Intrathecal pumps for delivery of antispasticity medications (eg, baclofen) can be implanted surgically.
 Severe neuropathic pain - Rhizotomy

PT GOALS
y Improve the ability to perform ADLs. y Improve the performance levels in employment, recreation

or leisure activities.
y Coordinating care with caregivers and other proffessionals. y Reducing the risk of secondary impairments. y Maintain joint integrity and mobility. y Increase strength, power and endurance. y Improve postural control.

y Improve motor funtion. y Decrease pain. y Improve locomotion, gait and balance. y Increase aerobic capacity. y Patient and family awareness. y Activity pacing and energy conservation techniques.

INTERVENTIONS
SENSORY DEFICITS & SKIN CARE
 Increase awareness of sensory deficits.  Compensate for sensory loss. Example , visual

compensation when prorioceptive loss produces imbalance and places the patient on risk of fall.
 Sensory deficits may remit, ongoing assessment is

necessary.
 Patients with prorioceptive involvement demostrate

impairment in movement control and motor learning so, augmented feedback is required like :

 Tapping Verbal cueing Biofeedback  Proprioceptive loading through exercise, resistance. For visual loss : Reduce clutter in environment Increase contrast Adequate night lighting

PAIN  Assessment of the cause of pain, musculoskeletal or joint malalignment.

Regular streching Massage Exercise Ultrasound Postural correction Correction of faulty movements with orthotic devices. Pool therapy has beneficial effect on painful paraesthesias. Pressure stockings and gloves.

 Stress management techniques: Relaxation Meditation Yoga

SPASTICITY
 Topical cold (ice packs, wraps, cold bath & sprays) reduces

spasticity by :
Decreasing tendon reflex excitability. Clonus Slowing conduction of impulses in nerves & muscles.  Sustained streching (manual or static splinting).  Deep pressure.  Side lying position well supported by pillows is very convenient

since it avoids stimulation of the tonic labyrinthine reflex and also, as head and trunk are in alignment, the stimulation of the asymmetrical tonic neck reflexes.

 Trunk rotation produces lower limb to extend, abduct and

externally rotate.
 Other factors such as quick movements, abruptly

performed, noisy surroundings, anxiety, excitement, over exertion should also be avoided as it may increase spasticity.
 Weight bearing postures are used to provide inhibitory

pressure.
 Slow Maintained Vestibular Stimulation :
Rocking chair Swiss ball Equilibrium board

 Proprioceptive Neuromuscular Techniques : Rhythmic Initiation Rhythmic Rotation

FATIGUE
 Avoid overwork & development of fatigue.  Modify tasks or environment for successful completion

of daily activities.
 Periods of activity interspersed with periods of rest.

 PARESIS Strengthening of affected muscle groups. Strengthening of muscles used for assistive devices. Submaximal exercise intensity. More repetitions. Exercise balanced with rest periods. Exercise in mornings. Strengthening of proximal muscles. PNF patterns.

ATAXIA
 Postural stability promoted by static holding in different weight

bearing positions like :

Prone on elbows Quadruped Kneeling  Progression by varying postural demands.  Joint approximation.  Rhythmic stabilisation (PNF)  Frenkels exercise.  Dynamic balance control.  Pool therapy for static & dynamic postural control.

 Velcro weight cuffs, weighted jackets, weighted canes.

(for dysmetric movements.)

 Theraband resistance.

FUNCTIONAL TRAINING
 Bed mobility  Transfers  Wheelchair use

AMBULATION
 AFO foot drop, poor knee control, spasticity.  Canes, crutches, wallker compensate for balance

problems.
 Wheelchair increasing fatigue levels.

CARDIORESPIRATORY FITNESS
 Medically supervised exercise tolerance test

(submaximal testing).
 FITT  Circuit training  Outcome measures : BP, HR, continuous ECG, Borgs

RPE.

COGNITIVE TRAINING
 Memory book  Pill dispenser  Posted schedule  Audiotapes  Cueing devices alarm clock  Labeled cabinets  Written instructions  Broken down tasks

PSYCHOSOCIAL ISSUES
 Patient issues  Caregivers issues

THANK YOU