POST-SURGERY RECOVERY

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What can I teach in 15 min?

• Update on statin myopathies.
• What to consider when a diagnosis of
  inflammatory myopathy is not responding.
• Do not miss IBM.

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Case 1 Lumber Jack!

• 69 y RHD male.
• PMHx
• Angioplasty 1995
• Meds Simvastatin, ASA, atenolol, terazocin, vits
  B/C/E
• HPI tree cutting x 2 DOMS w/ CK to 4869
  then dropping to 341 over 2 d.

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Statins and myopathy.

• 3 - 5 of patients develop myalgias.
• 0.1 rhabdomyolysis (10 X ULN).
• ? direct toxicity (phrenylation, COQ10).
• Recently there is evidence of delayed onset
  necrotic myopathy responsive to immunomodulation
  (Amato, M and N Mammen, AL, Arthritis and
  Rheum, 63713-, 2011) induce expression of
  anti-HMGCR autoanitbodies.

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Statin myositis.

• 100 of patients had myonecrosis.
• 20 showed inflammation.
• MOST of the patients in both studies responded to
  MTX and prednisone.
• 27/28 of our patient IDed in past 4 years
  responded to MTX and prednisone - one needed
  pulse solu-medrol and IgG.
• 50 of our patients had inflammation in biopsy.

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Case 2- Calf atrophy

• 26 y old male with difficulty getting up from
  squat age 19 y gt progressive.
• Family history - parents are consanguinous
  (paternal great grandmother is sister to his
  maternal great grandmother), one sister with
  similar phenotype and brother sister no weakness.
• Examination MS/CN N MOTOR minimal proximal
  UE weakness, profound calf gt anterior lower leg
  atrophy and weakness with hip flexors 2/5 and
  hamstrings 3/5.

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Case 2- Calf atrophy.

• Muscle biopsy inflammation, N - dysferlin.
• CK gt 3,000 iU.
• EMG fibrillations, PSW, myopathic.
• Dx inflammatory myopathy - no response to
  corticosteroids.
• Rheumatologist wanted a second opinion.
• Patient wanted to know about Rx options.

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Case 2 New mutation

• Calf atrophy - whole DYS gene sequenced.
• Mutation analysis c.4747 TgtG transversion
  (homo) p.Tyr1583Asp.
• Athena Since these types of sequence variants
  are similar to those observed in both
  disease-associated mutations and benign
  polymorphisms, the nature of this variation
  precluded clear interpretation.
• in silico evaluation
• SIFT not tolerated
• PolyPhen probably damaging, score 3.024.
• Tyr tyrosine is highly conserved 46/46
  vertebrata.
• Treatment
• Vitamin D 30 nmol/Ltestosterone N.
• Creatine monohydrate (0.1 g/kg/d).

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Case 2- Molecular issues

• Athena claims that they can detect 99 of DYS
  cases with a blood lyphocyte Western blot.
• We found that the immunohistochemistry was normal
  in this case and many others.
• We ran Western blotting and found none, reduced,
  normal and overexpression in 9 cases.
• Muscle Nerve. 2013 May47(5)740-7. Dysferlin
  aggregation in limb-girdle muscular dystrophy
  type 2B/myoshi myopathy necessitates mutational
  screen for diagnosis.
• Nilsson MI, Laureano ML, Saeed M, Tarnopolsky MA.

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Physical Exam - Clues to a genetic myopathy.

• Complete Neurological Exam.
• Cataracts, myotonia (DM1).
• Ptosis (MG, OPMD, mito).
• PEO (MG, mito, RSS).
• Calf atrophy (DYS, hIBM).
• Calf hypertrophy (BMD, LGMD)
• MSK exam
• FSHD may get rotator cuff issues.
• Contractures (Bethlem).

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Case 3 Skinny Legs

• Male 65 y.
• Slowly progressive thigh weakness.
• CK 1,200
• EMG mixed pattern

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IBM

• More common in older men.
• Quadriceps and finger flexor atrophy.
• CK is elevated but mild/moderate.
• EMG is often distinct from others.
• Swallowing affected in about 70 .
• Biopsy shows rimmed vacuoles ( aB crystallin,
  tau, APP) COX ve.

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When to send for further testing.

• No cause for the high CK.
• Neurological exam is abnormal (beyond
  radiculopathy or diabetic neuropathy).
• Any CK over 1,000 iU/L.
• Positive family history of high CK or NMD or
  arrhythmia/pacer or non-hypertensive
  cardiomyopathy (lamin A/C, BMD)(HOCM screen _at_
  CHEO).
• SOBOE weakness (Pompe, MG, LGMD, mito.).
• Sitting/supine FVC - gt 20 drop diaphragm weak.

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Thanks

• The clinic
• Ms. L. Brandt
• Ms. Erin Hatcher
• Ms. L. Brady
• Ms. D. Johnston
• Ms. H. Vey
• Ms. K. Scott
• The lab
• Dr. M. Nilsson
• Dr. M. Akhtar
• Dr. L. MacNeill
• Mr. D. Ogborn
• Collaborators
• Dr. B. Lach
• Dr. J. Provias
• Dr. J. Bourgeois
• Dr. T. Hawke
• Dr. J. Schertzer

• Warren Lammert and Family
• CIHR Institute of aging.
• McMaster Childrens Hospital and Hamilton
  Health Sciences Foundation.