New Prospects in Multiple Sclerosis

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"New Prospects in Multiple Sclerosis"

• Problem-oriented MS treatment with a positive spin

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Problems, Problems, More Problems!!
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Strategy

• Divide and Conquer

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Problems have solutions

• Optimism
• Collaboration between patient and physician

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Experience ProvesOptimism wins out over
pessimism
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Optimism vs. Pessimism

• Optimistic Persons do better clinically
• are they optimistic because they feel better or
  do they feel better because they are optimistic??
• Optimists are willing to explore possibilities
• Keep trying
• Dont reject therapies that may help
• Work with their professionals
• bring up issues pertinent to quality of life

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Optimism Rationale

• It works better
• More effective treatments than before
• New effective treatments on Horizon

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MS interrupts pathways
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Attack inflammation
Series of MRI scans in one patient
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Inflammation

• MS attack Area of inflammation
• One or more Areas in the Nervous system is
  inflamed

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Problem Reducing inflammation

• Acute attack
• Preventing attack

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Acute Attack

• Steroids
• Solu-Medrol intravenous
• Prednisone
• ACTH

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Preventing attack/progression

• Interferons
• Betaseron
• Avonex
• Copaxone
• Immune-suppressing drugs
• Methotrexate, Imuran

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Interferons

• Betaseron, Avonex
• Cut attacks by about one third
• Flu-like side effect
• ?Depression
• Hold in pregnancy

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Interferons

• Avonex
• Convenient once a week injection
• intra-muscular
• shown to decrease disability progression
• More minimal side effects ?lower dose

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Interferons

• Betaseron
• First to be introduced
• injected subcutaneously every other day
• Highest dose interferon
• more pronounced side effects
• some skin reactions
• start slow and with anti-inflammatory meds

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Copaxone

• Novel Mechanism of action
• Every day sq injection
• Very well-tolerated
• ? As much MRI effect
• ? Effect on Disability

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MS Issues

• Neuromuscular function
• Gait
• Vision
• Nutrition
• Bladder Function
• Sexual Function

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MS Issues (contd)

• Pain/Paresthesia
• Energy
• Spousal/ Social/Relationships
• Psychiatric
• Cognition
• Spiritual Needs

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Neuromuscular Function/probs

• Weakness
• Fatigue
• Spasticity
• Incoordination
• tremor
• Ataxia
• Dyscontrol

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NM Fxn/ Weakness/solns

• Attack Treat Inflammation
• Steroids, longer acting agents
• Physical Therapies
• Increase strength, endurance
• Movement Strategies
• Assistive Devices
• Occup. Therapy increase function

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NM/ Fatigue

• Causes more Weakness
• ?Due to prolonged inflammation
• ?similar to prolonged viral illness (cold)
• Something in the blood causes fatigue
• Damage to nerve fibers is not as important
• ? Does more fatigue mean more inflammation
• Does fatigue affect prognosis?

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NM/Fatigue/Solns

• Drugs
• Amantadine
• Activating antidepressants
• Prozac, Wellbutrin
• Stimulants
• Ritalin, Cylert,
• 4-Aminopyridine

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NM/Fatigue/Solns

• Exercise
• Preemptive - Goal to increase Stamina
• Budgeting Energy
• Energy-Saving Strategies

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NM/Spasticity/Why?

• Nervous system Control through INHIBITION
• Brain connection to spinal cord inhibits reflexes
• Connections are broken
• Reflexes are dis-inhibited (liberated from higher
  control
• Reflexes are increased
• SpasticityResistance to Motion Tightness

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NM/Spasticity/Solns

• Physical/occup Therapies
• Limbering loosening up
• Drugs
• Baclofen
• Tizanidine (Zanaflex)
• Valium
• Dantrium
• Botox

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Baclofen
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Baclofen Pump
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NM/incoord./problem

• Disconnection of
• Cerebellum
• Other motor areas
• Tremor
• Postural trunk and head
• in arms and legs
• Disorganization of Movement

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NM/Incoor/Sols

• Physical Therapy
• Movt Strategies and Synergies
• Assistive Devices
• Drugs
• Tremor
• Coordination
• anti-spastic

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NM/Tremor/Surgery

• Thalamotomy/Pallidotomy
• Tremor pacing device

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Activa tremor implant
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tremor device

• placed in the VIM of thalamus

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Gait/Problems

• Weakness
• lowers affected more than uppers
• Control
• Loss of Balance
• Ataxia

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Gait/Weakness

• Therapy
• Exercise for muscle strengthening
• Stretches and Drugs for Spasticity

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Gait/Balance

• Usually temporary
• Balance Exercises
• cane /walker
• vestibular medications
• attention to incoordination

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Vision

• Loss of Vision in one eye (optic Neuritis)
• Double Vision
• Problems in coordinating moving eyes
• Complex visual perceptive problems

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Vision

• Fortunately most problems are temporary

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Nutrition

• Regular well-balanced diet recommended
• Low saturated fats
• Vitamin Supplement
• Avoid Obesity

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Bladder

• Spastic Bladder
• Flaccid Bladder
• Dyssynergia

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Bladder/Spastic

• Bladder is small and tight
• urgency, frequency
• many voids with small volumes
• Goes with spasticity in legs
• Ditropan (XL), Detrol

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Bladder/flaccid

• Late in disease and less frequent
• Bladder is large and empties poorly
• Chronic change
• Intermittent Catheter usually recommeded

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Bladder dyssynergia

• Sphincter and bladder contract together
• Trouble pushing urine out against a closed
  sphincter
• Training and medication that affects contraction
  of both elements

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Sex

• Complex Issue
• Psychiatric aspects
• Anxiety
• Performance
• Relational
• Physical Issues
• Motor dysfunction
• Sensory Loss
• Assd with bladder/ spinal cord

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Sex (Sols)

• Drugs
• Newer agents
• Stopping certain drugs
• Relational (counseling)
• Techniques
• Methods to get around specific problems
• Openness!!

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Energy

• Chronic effect of inflammation
• ?Viral Illness?

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Energy (Solutions)

• Exercise (Incr. Stamina)
• Amantadine
• Activating Antidepressants
• Stimulants
• anti-inflammatories
• 4-AP

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Cognition More common than previously realized

• Attention
• Concentration
• Short-term memory
• Information Processing
• Executive Function/Organization
• Perception
• Speech
• 50 of patients

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Lesion Burden
More lesions Greater Effect
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Less lesion burden
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Cognition - solutions

• Problems with thought dont make you less of a
  person
• Just like a limp or problem with vision you have
  to get around.

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Cognition Sols 2

• Aids
• Notes
• Organizers
• Alarms
• Keyboards
• Personal Assistants

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Cognition- sols 3 Let people know...

• You are not goofing off
• You still care about your work
• Slowness of decision making does not make you
  indecisive
• If you are distractible it is not because you
  dont care

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Paresthesias

• Discomfort to severe pain
• Painful tonic spasms
• Anticonvulsants
• Tegretol, Dilantin, Neurontin
• Antidepressants

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Psychiatric

• Reaction to chronic disease
• Reaction to other persons reaction
• spouse
• employer
• other
• Direct effect of MS on brain
• Effect of other meds especially interferons

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psychiatric

• Talk it out
• support groups
• avoid whipping yourself
• help with medication
• Developing outlets
• pleasures
• hobbies
• purpose

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Spiritual Needs

• Developing a personal context
• Creating a network of acquaintances or one
  empathic person
• Refuse to be defined by your illness
• Taking charge

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Recent Advances
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New Treatments

• Immunomodulators
• Antibody Therapies
• Pumps
• New Drugs
• Devices

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Rebif study

• Positive results were reported from a large
  clinical trial in Europe, Canada and Australia of
  interferon beta-1a (Rebif) in relapsing-remitting
  MS. The drug reduced relapse rate, slowed
  progression of disability and reduced
  MRI-detected brain lesions. Ares-Serono is
  seeking approval of the drug from the FDA.

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Betaseron in progressive MS

• A large European clinical trial of interferon
  beta-1b (Betaseron) in over 700 people with
  secondary-progressive MS was stopped early
  because the study showed the drug can slow the
  progression of disability. The U.S. FDA is
  reviewing study findings for possible approval of
  Betaseron for this new use

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Monoclonal Antibodies

• Researchers across the U.S. continued or began
  separate clinical trials of two monoclonal
  antibodies (LeukArrest, by ICOS Corp. and
  Antegren, by Athena Neurosciences) aimed at
  reducing the severity and duration of MS attacks
  by blocking the entry of destructive immune cells
  into the brain and spinal cord.

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Antegren

• Elan drug
• monoclonal antibody
• attaches to alpha 4 Integrin
• protein on lymphocyte
• protein is receptor for lymphocyte attachment to
  blood vessels

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Antegren (Elan)

• monoclonal human antibody
• 12 week study in England
• reduction in brain lesions

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LeukArrest (monoclonal Ab)
Prevents White cells from invading brain
Red areas myelin breakdown
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Oral interferon

• Researchers at the University of Texas Health
  Science Center began a small-scale clinical trial
  of an oral form of interferon alpha for
  relapsing-remitting disease, based on positive
  findings in rodents with MS-like disease

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TCR (t-Cell receptor) peptide (Connetics)

• vaccine against t-cells

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Growth Factors

• Insulin-like growth factor
• Increase myelin
• When and where to implant

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Stem Cell Transplants

• May be more effective for diseases that kill
  neurons or brain cells
• One day may be effective for treating certain
  persons with MS

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Herpes 6

• Roseola in toddlers
• erythema subitum
• rash
• neurologic symptoms
• mononucleosis like in adults
• can invade CNS

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HHV-6

• Demyelinating when invades CNS
• Detected high levels in MS CNS (Challoner)
• Detected in bloodstream in MS patients
• Also seen in chronic fatigue

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HHV-6 Treatment

• Similar to Cytomegalovirus
• Ganciclorir and Foscarnet
• Gan can affect WBCs
• Fos can affect Kidneys anemia, lytes
• ?How long to treat?

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HHV-6 tests

• Peripheral blood test
• Shell vial Culture
• HerpesVirus Diagnostics Inc
• c/o Federal Express, 11101 W. Plank Court,
  Wauwatosa, WI 55226
• 270.00