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What can I teach in 15 min?

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. Case # 1– Lumber Jack!. 69 y RHD male. PMHx : Angioplasty – 1995 Meds : Simvastatin , ASA, atenolol, terazocin, vits B/C/E

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What can I teach in 15 min?

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  1. 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.

  2. 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.

  3. 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, 63:713-, 2011) = induce expression of anti-HMGCR autoanitbodies.

  4. 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.

  5. Case # 2- Calf atrophy • 26 y old male with difficulty getting up from squat age 19 y > 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 > anterior lower leg atrophy and weakness with hip flexors = 2/5 and hamstrings 3/5.

  6. Case #2- Calf atrophy. • Muscle biopsy = inflammation, N - dysferlin. • CK > 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.

  7. Case # 2= New mutation • Calf atrophy - whole DYS gene sequenced. • Mutation analysis = c.4747 T>G 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/L;testosterone = N. • Creatine monohydrate (0.1 g/kg/d).

  8. Case # 2- Molecular issues • Athena claims that they can detect 99 % of DYS caseswith 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 May;47(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.

  9. 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).

  10. Case # 3– Skinny Legs • Male 65 y. • Slowly progressive thigh weakness. • CK = 1,200 • EMG = mixed pattern

  11. 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 (+ αB crystallin, tau, APP) + COX –ve.

  12. 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 @ CHEO). • SOBOE + weakness (Pompe, MG, LGMD, mito.). • Sitting/supine FVC - > 20 % drop = diaphragm weak.

  13. 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 Children’s Hospital and Hamilton Health Sciences Foundation.

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