Myopathy, myasthenia Flashcards
Genetics on myotonic dystrophy type 1
Commonest inherited AD neuromuscular disease
Mutation in myotonin protein kinase(DMPK) Chr 19q
Triplet repeat disorder(CTG), anticipation with expansion of repeats
Clinical features of myotonic dystrophy
Weakness distal>proximal Wasting SCM, temporalis Frontal balding Intellectual impairment Diabetes/insulin resistant, hypogonadism, hypopituitary Cataract Cardiac conducn defects, cardiomyopathy later Respiratory, swallowing difficulty
Lipid storage myopathy features
CPT II Deficiency is the commonest cause of familial metabolic cause of rhabdomyolysis
Muscle bx -can be normal/minor lipid accumulation
Precipitated by prolonged moderate exercise/ fasting
Dx- tissue assay
Mx-Increase CHO, medium chain TG in diet
Glycogen storage myopathy features
Precipitated by brief high intensity exercise
Eg Mc Ardles’s disease
Duchenne muscular dystrophy features
Pathogenesis - abnormal dystrophin-abnormal muscle fibres
Eteplirsen -triggers excision of exon 51-restores dystrophin positive fibres
Spinal muscular atrophy features
Rare NM disorder with loss of motor neurons in spinal cord
Recessive, mutation in SMN1(high in CNS,kidney,liver) on 5q
Severity mediated by copy no of back up SMN2 gene
MC genetic cause of infant death
Nusinersen -increases prod of normal SMN protein
Nusinersen in SMA MOA
Antisense oligonucleotide binds to mRNA in intron 7 sequence
Reduces deletion of exon 7, increases prod of normal SMN
Increases strength, achievement of motor milestones, rates of mech ventilation and overall survival
What are the autoimmune myopathies
Polymyositis, dermatomyositis,immune mediated necrotising myopathy, inclusion body myositis
Clinical features of PM,DM,IMNM
Females>males, Weakness: proximal, Onset: sub a/c Muscle enzymes elevated EMG :irritable myopathy MRI :evidence of inflammation Muscle biopsy: inflammation, necrosis Responsive to immunosuppressive Rx
Characteristic pathology in DM
Perifascicular atrophy
Characteristic pathology in PM
Primary inflammation. Normal muscle fibre surrounded and invaded by CD8 Tcells.
Pathology in IMNM
Degeneration and regeneration with minimal inflammation
Muscle Bx findings in IBM
Classic finding -inclusions of rimmed vacuoles in muscle fibres
Autoantibody found in sporadic IBM
Cytosolic 5’nucleotidase 1A(NT5-C1A)
Abundant in skeletal muscle
May be involved in DNA repair
Prognostic marker as well -predicts severe motor, bulbar and respiratory involvement
Clinical features of antiHMG-CoAR myopathy
Bx- nectrotising in 80% patients Nearly 100% proximally weak 75% myalgias CK -10000 max Upto 70% associated with statin exposure Requires immunosuppressive Rx Progresses despite ceasing statin
