Proximal Muscle Weakness Myopathy Or Myositis The Case 53 yo male, lives in boarding house Readmitted after recent discharge with c/o myalgias, weakness and falls PMHx COPD – many admissions, more so this year, usually treated with steroids, bronchodilators and antibiotics, still smokes The Case PMHx cont’d PE – 2002, now on Coumadin Nephrolithiasis – 2000 Depression, remote appendectomy, Baker’s cystectomy No CAD, DM, HTN, stroke No Fam Hx of CTD, vasculitis, cancers Denies EtOH, or drugs, unprotected sex 6/12 ago The Case Meds Ventolin/ Atrovent/ Flovent Theodur Prednisone 50 po OD Losec, Clonazepam, Wellbutrin, Coumadin, Prozac NKDA The Case HPI Since Dec 2002, 4 admissions for AECB (2 at SMH) Treated with steroids each time Recent admission April 26 to May 10 First 60 mg IV solumedrol then po then stopped but flared so restarted on 50 Prednisone and tapered to off 3 days post discharge (total 17 days) The Case HPI cont… In hospital – no myalgias, weakness, unsteadiness On discharge – able to do all activities, limited by SOB Approx 3/7 post D/C felt “achy” in thighs then shoulders associated with tremor in upper extremities The Case HPI cont… Became progressively weaker over next week – unable to stand from toilet seat, get up from bed, but able to walk Started to fall, legs gave out, no presyncope, vertigo, LOC Up to 3 times a day, so came to ER Felt to also have AECB so started on steroids The Case HPI cont… Denies focal weakness, sensory deficit, dysphagia, headache, visual change No F/C/NS, rash, wt loss VSS, afebrile, 94% on r/a Neck supple, no scalp tenderness, no LN, normal thyroid O/E The Case O/E cont… Diffuse wheezes, decreased A/E, distant but normal HS, Abdo benign No hand or heliotropic rash, no active jts, normal ROM, tender quadriceps bilaterally Obvious quadriceps atrophy Deltoid 4/5, biceps 4/5, triceps 4-/5, hands 5/5, Hip F/E 4/5, Knee F/E 4/5, Feet 5/5 Reflexes normal (? brisk), sensation normal The Case Investigations Hg 133 (MCV 103.4), WBC 10.2, Plt 218 Lytes, Cr normal, Ca, P04, Mg normal TSH 0.3, fT4 12.4 fT3 CK 1074 1237 680 423 196 64 EMG possible polyneuropathy, no fasciculations, no myopathy detected Why is he weak? & Why is the CK high? Neuropathy, Myopathy Or Myositis? Neuropathy Pattern usually involves distal motor and sensory neurons > proximal Can be seen in anterior horn cell disease and NMJ disorders EMG shows fasciculations or amplitude loss Elevation of CK can be seen in AHC dz but not a common feature Based on history, physical and investigations the differential can be narrowed Inflammatory Polymyositis Usual insidious onset (3-6/12) with no precipitant Shoulder and girdle most affected, neck in ~50%. Dysphagia and dysphonia can develop Myalgias and arthralgias not uncommon but severe tenderness and synovitis are unusual Inflammatory Polymyositis CK is usual elevated at some point but may be normal early or with advanced atrophy EMG reveals: ^ insertional activity, spont bizarre high-frequency discharges, polyphasic MUP of low amplitude 10-15% have normal EMGs Biopsy – necrosis and regeneration with T cell infiltrate Inflammatory Polymyositis Associated with auto-antibodies to aminoacyl-tRNA synthetases (anti-Jo-1) Mainstay of treatment is steroids – initial Prednisone @ 0.5-1.5mg/kg/day MTX and Imuran also affective Associated with cancer – 6-fold with DM (15%) and 2-fold with PM (9%) Inflammatory Inclusion body myositis Affects older ages (mean 60yo) Symptoms present for 5-6yrs prior to Dx Proximal lower ext usually prior to upper Usually symmetric but asymmetric in 1015%. Myalgias in ~40% CK normal or mildly elevated (<10X norm) EMG similar to PM, may have nerve changes Inflammatory Inclusion body myositis MRI can help - involvement of the deep finger flexors occurs early in the course of the disease; demonstrated in almost 95% Biopsy - Basophilic-rimmed vacuoles within the muscle fiber sarcoplasm in virtually all patients; filamentous inclusions and vacuoles on electron microscopy Inflammatory Inclusion body myositis Treatment – no good role for steroids; MTX and Imuran have little effect, small effect from IVIG Myositis can be a feature of SS, SLE, MCTD, Sjogrens > RA, AOSD, WG and PAN Metabolic Disorders of glycogen metabolism McArdle’s – def of myophosphorylase Usually exercise induced, usually develop in childhood May be associated with severe cramping and rhabdo Subset with proximal muscle weakness as adults Metabolic Disorders of glycogen metabolism Glycogen deposition on biopsy Forearm Ischemic Exercise test – venous lactate and NH3 levels pre and post tourniquet Disorders of lipid metabolism Carnitine deficiency – proximal muscles affected with ^CK and myopathy on EMG Mitochondrial myopathies Drug-Induced Steroids May occur shortly after onset of therapy or after years Subacute over weeks with proximal muscle weakness and wasting but usually not myalgias or tenderness Dose related – rare in <10mg/day; >40-60 usually results in some weakness Drug-Induced Steroids Glucocorticoids – direct catabolic effect on skeletal muscle via amino acid for gluconeogenesis Also interfers with ILGF-1 signaling increased myocyte apoptosis CK usually normal; EMG usually normal With reduction or D/C of steroids, ^ strength within 3-4 weeks Looking Back – this admission Date 18/5/03 18 18 19 20 22 CK 792 1074 1209 1237 698 447 History ++falls Started on 50mg Pred 23 24 25 423 312 196 28 64 Myalgias gone MRI High uptake in rectus femoris bilaterally, non-specific Upper extremities normal Did the steroids help him Or Is the CK from the falls? Looking Back–Prev admissions Date CK History 28/4/99 13/11/00 14 178 1937 1541 ER visit with L headache and c/p R flank pain- renal colic +AECB started on 18 15/12/00 15/11/01 27/08/02 27 27 1420 873 120 46 54 51 50 Pred Renal colic + SOB AECB AECB with h/a and Myalgias Pred 50 x 10/7 Looking Back–Prev admissions Date CK History 7/11/02 7 8 8 448 555 674 872 SOB with generalized Weakness, NX, F/C Pred with slow taper 13/12/02 24/3/03 24 26/4/03 26 152 64 80 88 57 AECB Rx steroids AECB Rx steroids AECB Rx steroids Is there a pattern? Should he be biopsied?