Muscle Diseases Flashcards
Type 1 muscle fiber stains
ATPase 4.3 - dark
NADH - dark
Type 2 muscle fiber stain
ATPase 9.4 - dark
Mitochondrial Staining
Gomori trichrome - ragged red fibers - accumulations of abnormal mitochondria
Cytochrome oxidase -
Glycogen Staining
PAS (Periodic Acid-Schiff)
Amyloid Stain
Congro Red
- Neurogenic atrophy is indicated by what muscle pattern?
- Separate grouping of muscle types rather than mixed presentation. “Type grouping”
Peripheral nerves sprout and reinnervate muscle. Atrophy resolves, but grouping occurs.
An infant is being evaluated for a motor neuron disease. Alpha (lower) motor neurons are degenerating resulting in panfascicular atrophy (fascicles atrophied w/ a few large fibers) and difficulty feeding. As patient develops, sitting up and other milestones are not reached. The survival motor neuron gene on chromosome 5 is deemed to be defective.
Spinal muscular atrophy
Autosomal recessive - SMN1 gene responsible, SMN 2 defect results in earlier onset
Forms: Types 0-4
-Werdnig-Hoffman (SMA Type 1) - most severe - w/in 4-6 months and death in 3 years
-SMA types 2 and 3 later onset/death
What are the features of myopathic muscle atrophy?
- Centralized nuclei
Proximal muscles > distal (muscle size is larger proximal)
Degeneration/regeneration process
Forms: Inflammatory, dystrophic (genetic), metabolic, congenital, toxic/drug - all have unique findings
Characteristics of inflammatory muscle atrophy? Antibodies? Progression? Other labs? Various conditions?
-Inflammation - lymphocytes
-Myonecrosis/myophagocytosis
-Proximal > distal weakness
-Elevated creatine kinase
-Anti-Jo-1 (tRNA synthetase) autoantibodies
Types:
Polymyositis, Dermatomyositis, Inclusion body myositis
What is a muscular dystrophy?
Genetic myopathy and progressive loss of muscle due to dystrophin protein
5y/o child presents with profound weakness. Calves appear hypertrophic - biopsy reveals muscle loss and fatty replacement of tissues. Beginning stages cardiomyopathy and some conduction abnormalities are noted. Genetic tests reveal either a large deletion or stop codon placement in Xp21 gene. Followup on the patient in his teens shows he is now in a wheelchair. Followup shows that he dies at 23.
Duchenne Muscular Dystrophy - genetic
25y/o male patient arrives w/ weakness that has progressed since he was in his teens. He has led a normal life. Muscle biopsy reveals enlarged fibers, degenerating (necrotic) fibers w/ regeneration, internal nuclei, and fibrosis around the muscle fibers (endomyosial). Cardiomyopathy is evident. Genetic testing shows Xp21 gene involvement.
Beckers Muscular Dystrophy - genetic
- Can live normal life
- Can live into old age w/o diagnosis
Dystrophinopathy
- Umbrella term for the classic forms of MD: Duchenes and Beckers.
- Dystrophin is a large, subsarcolemmal protein involved in structural support for cell membrane. Linked to actin and ECM. Coded on Xp21, hence, X-linked disease. 2/3rds genetic, 1/3rd sporadic.
Pt complains of progressive shoulder and pelvic girdle weakness. Similar familial complaints have been reported in his siblings/cousins. Autosomal pattern of inheritance present. Biopsy reveals dystrophin-associated proteins are dysfunctional in muscle fibers.
Limb-Girdle Muscle Dystrophy - genetic Autosomal dominant/recessive Due to dystrophin-associated proteins - Sarcoglycans - Lamin A or others Not X- linked
Aside from skeletal muscle weakness and an inability to relax contractions (myotonia), Pt. history reveals cataracts, baldness, testicular atrophy, cardiomyopathy, dementia, and glucose abnormalities. Biopsy reveals muscle fibers w/ increased numbers of internal nuclei (>4%) and rings in the muscle fibers (“Ringbiden”) w/ sarcoplasmic masses. Genetic testing reveals CTG repeat patterns and an autosomal dominant inheritance pattern.
Myotonic Dystrophy - genetic Atrophy Baldness Ccataracts Dementia Tonia Toupee Ticker (FA-73)
Adolescent/young adult M/F arrives complaining of cramping, fatigue, myalgia, and poor tolerance to exercise/endurance. Evaluation revels swollen muscles w/ fixed weakness. UA reveal myoglobinuria. Genetic testing reveals autosomal recessive mutation in glycogen phosphorylase gene on chromosome 11.
McArdle Disease
Large collections of glycogen in muscle cells - Autosomal recessive - mutations in gene coding glycogen phosphorylase on chromosome 11
(FA-99)
40y/o patient presents with progressive paralysis of the eye muscles and bilateral ptosis. Retinal pigmentary degeneration is apparent. EKG reveals cardiac arrythmia.
Kearns-Sayre Syndrome - mitochondrial myopathy (encephalomyopathy) - defect in mitochondrial gene coding for oxidative phosphorylation
Young female presents with stroke-like symptoms at the ER, but CT does not reveal stroke. She is discharged after many tests w/ no results. Primary care followups over years reveal many such episodes w/ slow development of dementia and encephalopathy.
MELAS - Mitochondrial encephalopathy w/ lactic acidosis and stroke-like episodes - Mitochondrial myopathy
Child presents w/ myoclonus and epilepsy. Ataxia develops as does myopathy. Study reveals ragged red fibers in mitochondrial cells.
MERRF - Myoclonic epilepsy
Ragged red fibers - mitochondrial myopathy
Congenital Muscle Atrophy Diseases are characterized at a young age with what statement? This indicates what? What is the progression? What are the 3 types and their characteristics?
“Floppy baby” - hypotonia and proximal or generalized weakness - early onset
- Slowly progressive or non-progressive
Nemaline Rod - Subsarcolemmal Z-band material
Centronuclear - abundant central nuclei
Central Core - Lightly eosinophilic areas in Type 1 fibers; NADH
Muscle biopsy reveals retention of checkerboard - no type grouping apparent, but Type 2 fibers on ATPase 9.4 are more atrophied than type 1. What toxin/drug caused this presentation?
Corticosteroids
Presentation consistent with inflammatory myopathy process.
Complaints of muscle pain/problems. What toxin/drug is likely causative agent?
Statins
Patient presents with rhabdomyolysis - muscle necrosis and inflammation; denervation is also present. What drug/toxin is the likely causitive agent?
Ethanol
Female adult presents with some complaints of weakness. Labs show autoantibodies for Anti-Jo-1 (tRNA synthetase). She recently had a viral infection. Biopsy reveals degenerating and regenerating fibers w/ myophagocytosis and inflammation distributed throughout the muscle fibers. Muscle fibers are presenting MHC-1 molecules and high density of CD8+ cytotoxic lymphocytes and macrophages. Potential heart, lung, and vessel involvement are being investigated. Follow up shows she is responsive to steroids.
Polymyositis
- Inflammatory -
Female child appears to have weakness. She presents with heliotrophe (lilac discoloration) of eyelids w/ periorbital edema and discolored knuckles, elbows, and knees. She has Hx. of interstitial lung disease, myocarditis, and vasculitis also. Labs reveal high CD4+ and 8+ lymphocyte ratio. Muscle biopsy reveals perifascicular atrophy. as well as some necrosis and regeneration of fibers. Patient responds well to steroids.
Dermatomyositis
- Inflammatory -
Elderly male evaluated for weakness. Inflammation presents w/ periorbital edema and discolored knuckles and knees. Muscle biopsy reveals vacuoles rimmed w/ basophilic material, tau and ß-amyloid deposition in the cytoplasm of muscle fibers. Pt. is treated w/ steroids and his condition worsens
Inclusion Body Myositis
- Inflammatory -
