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.

. y The disease presumably can be exacerbated by hormonal changes during the postpartum period. In fact. no etiologic agent for MS has been identified. only 1 of every 4 MS attacks is associated with an intercurrent infection.ETIOLOGY y Despite intensive efforts in finding the source of the disease. y Some argue that MS could be a heterogeneous disorder triggered or perpetuated by several different environmental agents.

 Highest incidence in US and Northern Europe.  It is believed to be a disease of Caucasians (light skinned people from Europe. Western Asia and India).DEMOGRAPHICS OF MS y Frequency  More than 2. .5 million people worldwide are estimated to be affected by multiple sclerosis. North African. People living closer to equator show lesser incidence of this disease.

 In India alone. .000 to 50. Which means that the attacks are mostly confined to optic nerve and spinal cord. MS in India has Optico-spinal phenotype (as generally reported in Asian population).000 people who are affected with MS. there are 40.

recurrent respiratory tract infections in bedridden patients due to difficulty in handling secretions).  People with MS usually die of complications related to MS disability rather than of MS itself (eg. .  Patients with MS are thought to have an average life expectancy 5-7 years shorter than that of the general population.Mortality/Morbidity  Multiple sclerosis causes considerable disability in the working age group.

 This ratio is even higher (3:1) among patients in whom onset of MS is before age 15 years or after age 50 years. Sex  Multiple sclerosis affects females more than males (1. suggesting a hormonal component to the disease process.6-2:1). . but the basis for this difference is unknown. by racial or geographic differences.  Disease severity or drug treatment effect variability may be accounted for. at least in part.Race  Multiple sclerosis presents more often in populations of northern European ancestry.

. Age  Multiple sclerosis most commonly afflicts people aged 18-50 years. while females tend to experience more relapses. but any age group can be affected. Males have a greater tendency to develop primary progressive MS.

An environmental agent or event (eg. chemicals.  These factors are in part environmental and in part hereditary: 1. a set of genes or polymorphisms) to result in immune dysfunction. lack of sun exposure) has been hypothesized to act in concert with a specific genetic predisposition (ie. . virus.CLINICAL FINDINGS IN MS y CAUSES  The cause of multiple sclerosis is unknown. Multiple factors are likely to act. bacteria.

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

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

allowing their entry through the blood-brain barrier (BBB). or B cells.PATHOPHYSIOLOGY OF MS  The mechanism of demyelination in multiple sclerosis may be activation of myelin-reactive T cells in the periphery. including interferon gamma and tumor necrosis factor alpha.  T cells are activated following antigen presentation by antigen- presenting cells such as macrophages and microglia. which then express adhesion molecules.  Antibodies against myelin also may be generated in the periphery or intrathecally. .  Perivascular T cells can secrete proinflammatory cytokines.

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.HISTORY y Attacks or exacerbations of multiple sclerosis are characterized by new symptoms that reflect CNS involvement. weakness of one or more limbs. optic neuritis. sensory symptoms). y These symptoms are typically separated in time (eg. y Recognizing that physical and cognitive disability progression in MS may occur in the absence of clinical exacerbations is important. by months or years) and in anatomical location (eg.

Staging of ms .

RELAPSING REMITTING MS (RRMS) y Patients who improve after acute attacks have relapsing remitting MS (RRMS). during the natural course of RRMS. . approximately 75-85% of patients enter a stage referred to as secondary progressive MS (SPMS). y However.

which gradually progresses to involve other limbs and may culminate in total paralysis. y Some of these patients first present with weakness of only one limb. accumulate disability faster than other patients. without remissions) from the time of disease onset.PRIMARY PROGRESSIVE MS (PPMS) y Patients with primary progressive MS (PPMS) tend to accumulate disability without interruption (ie. and tend to have more weakness of the legs as well as incontinence (a reflection of greater spinal cord involvement). y Patients with PPMS typically respond poorly to the current therapeutic options for MS. .

.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. or cerebellar symptoms. . cognitive.

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). in patients with a history of mild manifestations at onset. sometimes drastically. . y Making a diagnosis of benign MS too early during the course of the disease is discouraged since MRI and clinical activity can worsen.

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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.

Bowel habit changes may occur. whereby patients have difficulty controlling their emotions (laughing. variable weakness. y Patients with MS also commonly complain of numbness or tingling in one or more limbs. as those with paroxysmal qualities may respond better to specific treatments. y An often overlooked manifestation of MS is the pseudobulbar affect. y Urinary retention and incontinence are common. . crying) and are perceived to act inappropriately by coworkers or friends. but bowel incontinence is less frequent. or sensory level-related symptoms.y Painful limb syndromes are important to recognize.

premature ejaculation. impaired genital sensation .y Sexual dysfunction affects the great majority of patients with MS and includes symptoms such as lack of desire. erectile dysfunction. impaired sexual responsiveness.

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

    Glucose level is usually normal. WBC count can be slightly to moderately elevated . 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. Protein level can be normal or slightly elevated.INVESTIGATIONS y LAB STUDIES 1.

.  Patients with optic neuritis and longitudinally extensive spinal cord lesions by MRI should be tested for neuromyelitis optica (NMO). 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.2. searching for the presence of aquaporin 4 antibodies in the serum.

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

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reflecting the chronicity of the demyelinating process. .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.

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auditory. 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 . or somatosensory). 5. Evoked potentials  Evoked potential testing (visual.  the most sensitive are the visual evoked potentials (50-80% sensitivity). followed by the somatosensory potentials (5070% sensitivity).4.

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y Pemoline. .MEDICAL MANAGEMENT y Amantadine (Symmetrel) or Modafinil (Provigil) is often attempted when no contraindications exist.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.

high-frequency (HDHF). Glatiramer acetate SC [Copaxone] 4.y Immunomodulatory drugs Eg. Interferon beta-1a IM [Avonex] 2. y As a rule of thumb. . 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. 1. with the highest efficacy demonstrated in clinical trials for the high-dose. Interferon beta-1b SC [Betaseron and Extavia] 3. these drugs tend to decrease the rate of MS relapses by approximately one third.

.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.

mitoxantrone is typically reserved for patients with aggressive clinical presentations of MS (ie.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.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. worsening MS) or in whom immunomodulatory drug therapy has failed.  Mitoxantrone.

Baclofen. gabapentin (Neurontin). amitriptyline (Elavil) y Spasticity . intrathecal baclofen delivered via programmable pump y Painful tonic spasms .Fluoxetine (Prozac). sertraline (Zoloft). phenytoin .SYMPTOMATIC MEDICATION y Decreased walking speed .Baclofen. dantrolene.Dalfampridine (Ampyra) y Depression . tizanidine. diazepam (Valium). carbamazepine (Tegretol).

methylphenidate (Ritalin) y Urinary dysfunction . gabapentin. imipramine (Tofranil).Propantheline bromide (Pro- Banthine). intermittent self-catheterization y Tremors/ataxia . tadalafil (Cialis). vardenafil (Levitra). propranolol (Inderal).Modafinil. amantadine.Clonazepam (Klonopin).y Fatigue .Sildenafil (Viagra). tolterodine tartrate. weighted bracelets y Erectile dysfunction . primidone (Mysoline). oxybutynin (Ditropan). fluoxetine. alprostadil (Muse) .

SUGICAL MANAGEMENT y Surgical procedures that relate to multiple sclerosis are directed primarily at alleviating symptoms :  Dysphagia .Rhizotomy .gastrojejunal tube placement  Significant limb spasticity or contractures - Adductor leg muscle tendon release.  Severe neuropathic pain . baclofen) can be implanted surgically. Intrathecal pumps for delivery of antispasticity medications (eg.

y Reducing the risk of secondary impairments. power and endurance. . y Improve postural control. recreation or leisure activities.PT GOALS y Improve the ability to perform ADLs. y Coordinating care with caregivers and other proffessionals. y Increase strength. y Maintain joint integrity and mobility. y Improve the performance levels in employment.

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

visual compensation when prorioceptive loss produces imbalance and places the patient on risk of fall.INTERVENTIONS SENSORY DEFICITS & SKIN CARE  Increase awareness of sensory deficits. ongoing assessment is necessary.  Compensate for sensory loss. augmented feedback is required like : .  Sensory deficits may remit. Example .  Patients with prorioceptive involvement demostrate impairment in movement control and motor learning so.

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

PAIN  Assessment of the cause of pain. ‡ Pressure stockings and gloves. musculoskeletal or joint malalignment. . ‡ Pool therapy has beneficial effect on painful paraesthesias. ‡ Regular streching ‡ Massage ‡ Exercise ‡ Ultrasound ‡ Postural correction ‡ Correction of faulty movements with orthotic devices.

 Stress management techniques: ‡ Relaxation ‡ Meditation ‡ Yoga .

‡ Clonus ‡ Slowing conduction of impulses in nerves & muscles.  Sustained streching (manual or static splinting).  Side lying position well supported by pillows is very convenient since it avoids stimulation of the tonic labyrinthine reflex and also.  Deep pressure. . the stimulation of the asymmetrical tonic neck reflexes. wraps. as head and trunk are in alignment. cold bath & sprays) reduces spasticity by : ‡ Decreasing tendon reflex excitability.SPASTICITY  Topical cold (ice packs.

over exertion should also be avoided as it may increase spasticity. Trunk rotation produces lower limb to extend. abduct and externally rotate.  Slow Maintained Vestibular Stimulation : ‡ Rocking chair ‡ Swiss ball ‡ Equilibrium board . excitement. abruptly performed.  Other factors such as quick movements. anxiety.  Weight bearing postures are used to provide inhibitory pressure. noisy surroundings.

 Proprioceptive Neuromuscular Techniques : ‡ Rhythmic Initiation ‡ Rhythmic Rotation .

FATIGUE  Avoid overwork & development of fatigue.  Periods of activity interspersed with periods of rest. .  Modify tasks or environment for successful completion of daily activities.

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

 Pool therapy for static & dynamic postural control.  Rhythmic stabilisation (PNF)  Frenkel¶s exercise. .  Dynamic balance control.  Joint approximation.ATAXIA  Postural stability promoted by static holding in different weight bearing positions like : ‡ Prone on elbows ‡ Quadruped ‡ Kneeling  Progression by varying postural demands.

.)  Theraband resistance. weighted jackets. weighted canes. Velcro weight cuffs. (for dysmetric movements.

FUNCTIONAL TRAINING  Bed mobility  Transfers  Wheelchair use AMBULATION  AFO ± foot drop. spasticity.  Wheelchair ± increasing fatigue levels.  Canes. crutches. . wallker ± compensate for balance problems. poor knee control.

continuous ECG. .  FITT  Circuit training  Outcome measures : BP. Borg¶s RPE.CARDIORESPIRATORY FITNESS  Medically supervised exercise tolerance test (submaximal testing). HR.

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 .

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