RECENT ADVANCES IN TREATING POST-POLIO SYNDROME

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RECENT ADVANCES IN TREATING POST-POLIO SYNDROME

• Susan L. Perlman, M.D.
• Associate Professor of Neurology
• UCLA Medical Center

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CURRENT LITERATURE32 CITATIONS SINCE 5/00

• CAUSES OF POST-POLIO SYNDROME
• FATIGUE
• BRAINSTEM NEURONAL INJURY
• ANIMAL MODELS
• DRUG TRIALS
• STEM CELL RESEARCH
• HOW ARE PEOPLE DOING

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WHAT PPMA IS AND IS NOT (I)

• It has not yet been shown to have genetic risk
  factors (Bartholdi et al., SMA gene nl.
  Neuromuscular Disorders 1099, 2000)
• Similar delayed progressive decline seen in
  survivors of other conditions (myelopathy) that
  injured anterior horn cells (metabolic overload
  of enlarged or fragile motor units)
  (Narayanaswami et al., J Neurol Sci 18411, 2001)

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WHAT PPMA IS AND IS NOT (II)

• It is not just normal aging of the motor units.
  Taiwanese polio survivors are 10-20 years younger
  than Western patients at onset of post-polio
  symptoms (Chang et al., Spinal Cord 39526, 2001)
• There were no publications addressing the role of
  the immune system or the effects of other
  infections or medical conditions.

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WHAT PPMA IS AND IS NOT (III)

• What about persistant polio virus? Dalakas
  feels that leftover pieces of the old virus may
  still be present in the nervous system, causing
  an immune reaction, but not ongoing
  infection. Girard, et al., have shown in mice
  that viral RNA does not replicate and infect, but
  may persist in an altered form (J Gen Virol
  831087, 2002)

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FATIGUE (I)

• While not the hallmark of PPMA, is by far the
  most common symptom (gt80).
• Klein, et al., studied 120 patients and reported
  decreasing strength, at a rate higher than normal
  aging and in upper extremities and flexors of the
  leg (repetitive stepping muscles, not
  weight-bearing) (Arch Phys Med Rehabil 811059,
  2000)

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FATIGUE (II)

• Sunnerhagen, et al., discuss several types of
  fatigue in PPMA (Acta Physiol Scand 171335,
  2001) central fatigue emotional
  fatigue fatigue from deconditioning
  augmented peripheral fatigue (enlarged muscle
  fibers that activate more slowly, contract less
  well, or recover abnormally)

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BRAINSTEM NEURONAL INJURY (the basis of much of
Brunos work)

• Bruno (Am J Phys Med Rehabil 794,
  2000) non-paralytic polio did cause neuronal
  lesions and these survivors are at risk for PPMA
  (14-42)
• Bruno, et al., also discussed word-finding
  difficulties in 79 of survivors with fatigue,
  documented by psychological testing and
  associated with decreased brain dopamine (ibid.,
  79343, 2000)

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NEW TECHNOLOGIES

• Trojan, et al., at the national neurology
  meetings in April 2002, presented the use of
  magnetic resonance spectroscopy to assess
  neuronal number and metabolism in fatigued polio
  survivors. Neuronal loss and dysfunction was
  found in the brainstem (reticular activating
  system), but not the temporal lobes, discounting
  a generalized brain problem as a cause of PP
  fatigue.

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ANIMAL MODELS

• Efforts have been ongoing to develop PPS animal
  models that can be used to study disease
  progression and treatment response.
• Rats with partially injured/enlarged motor units
  were seen to lose axon terminal connections with
  time and with repetitive exercise (Tam et
  al., Muscle Nerve 25359, 2002)

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DEVELOPING DRUG TRIALS (I)

• Nollet, et al., at the national neurology
  meetings in April 2002, presented another
  randomized, double-blind, placebo-controlled
  study of pyridostigmine (Mestinon 60mg four times
  per day) in 67 patients with abnormal
  single-fiber EMG studies. Results were assessed
  at 5 and 14 weeks.

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• Subjective fatigue, isometric strength, and EMG
  did not improve.
• Timed walking performance improved about 5-6 on
  Mestinon, mainly in patients with normal sized
  motor units (wiring was there, but connections
  were faulty).
• Confirms the prior report by Trojan (Neur
  531225, 1999)--helpful, but not compelling

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DEVELOPING DRUG TRIALS (II)

• Trojan, et al., in a study of 112 survivors found
  insulin-like growth factor levels did not
  correlate with strength and may not be a cause of
  fatigue in PPMA (J Neurol Sci 182107, 2001)
• MRS can detect levels of lipids, creatine, and
  carnitine in muscle fibers and may be useful in
  trials of new drugs or rehab and in studies of
  causes of PPMA (Jagannathan et al., Magn Reson
  Imaging 20113, 2002)

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HOW ARE PEOPLE DOING?

• More publications indicate that polio survivors
  are best served in multidisciplinary clinics
  staffed by knowledgeable professionals.
• Polio survivors report poorer functional status
  and health-related quality of life.
• The life-altering effects of PPMA have not been
  adequately addressed by health care providers.

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EDUCATIONAL IMPERATIVE

• The March of Dimes has issued a report for
  physicians that outlines the best practices in
  diagnosis and care of post-polio syndrome.
• This report has been publicized by the American
  Medical News and has been reprinted in the
  Medical Board of California ACTION REPORT, which
  is mailed to all physicians licensed in
  California.

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