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
CK 792
1074 1209 1237
History ++falls
Started on 50mg Pred
20 22
23 24
698 447
423 312
25 28
196 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 28/4/99
13/11/00
CK 178
1937
History ER visit with L headache and c/p
R flank pain- renal colic
14 18 15/12/00 15/11/01
27/08/02 27 27
1541 1420 873 120
46 54 51
+AECB started on 50 Pred Renal colic + SOB AECB
AECB with h/a and Myalgias Pred 50 x 10/7
Looking Back–Prev admissions
Date 7/11/02 7
8 8 13/12/02
CK 448 555
674 872 152
History SOB with generalized Weakness, NX, F/C
Pred with slow taper AECB Rx steroids
24/3/03 24 26/4/03 26
64 80 88 57
AECB Rx steroids AECB Rx steroids
Is there a pattern? Should he be biopsied?