Muscle Diseases

Question 1

Type 1 muscle fiber stains

Answer 1

ATPase 4.3 - dark

NADH - dark

Question 2

Type 2 muscle fiber stain

Answer 2

ATPase 9.4 - dark

Question 3

Mitochondrial Staining

Answer 3

Gomori trichrome - ragged red fibers - accumulations of abnormal mitochondria
Cytochrome oxidase -

Question 4

Glycogen Staining

Answer 4

PAS (Periodic Acid-Schiff)

Question 5

Amyloid Stain

Answer 5

Congro Red

Question 6

1. Neurogenic atrophy is indicated by what muscle pattern?

Answer 6

1. Separate grouping of muscle types rather than mixed presentation. “Type grouping”
   Peripheral nerves sprout and reinnervate muscle. Atrophy resolves, but grouping occurs.

Question 7

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.

Answer 7

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

Question 8

What are the features of myopathic muscle atrophy?

Answer 8

• 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

Question 9

Characteristics of inflammatory muscle atrophy? Antibodies? Progression? Other labs? Various conditions?

Answer 9

-Inflammation - lymphocytes
-Myonecrosis/myophagocytosis
-Proximal > distal weakness
-Elevated creatine kinase
-Anti-Jo-1 (tRNA synthetase) autoantibodies
Types:
Polymyositis, Dermatomyositis, Inclusion body myositis

Question 10

What is a muscular dystrophy?

Answer 10

Genetic myopathy and progressive loss of muscle due to dystrophin protein

Question 11

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.

Answer 11

Duchenne Muscular Dystrophy - genetic

Question 12

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.

Answer 12

Beckers Muscular Dystrophy - genetic

• Can live normal life
• Can live into old age w/o diagnosis

Question 13

Dystrophinopathy

Answer 13

1. Umbrella term for the classic forms of MD: Duchenes and Beckers.
2. 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.

Question 14

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.

Answer 14

Limb-Girdle Muscle Dystrophy - genetic
Autosomal dominant/recessive
Due to dystrophin-associated proteins
- Sarcoglycans
- Lamin A or others
Not X- linked

Question 15

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.

Answer 15

Myotonic Dystrophy - genetic
Atrophy
Baldness
Ccataracts
Dementia
Tonia
Toupee
Ticker
(FA-73)

Question 16

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.

Answer 16

McArdle Disease
Large collections of glycogen in muscle cells - Autosomal recessive - mutations in gene coding glycogen phosphorylase on chromosome 11
(FA-99)

Question 17

40y/o patient presents with progressive paralysis of the eye muscles and bilateral ptosis. Retinal pigmentary degeneration is apparent. EKG reveals cardiac arrythmia.

Answer 17

Kearns-Sayre Syndrome - mitochondrial myopathy (encephalomyopathy) - defect in mitochondrial gene coding for oxidative phosphorylation

Question 18

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.

Answer 18

MELAS - Mitochondrial encephalopathy w/ lactic acidosis and stroke-like episodes - Mitochondrial myopathy

Question 19

Child presents w/ myoclonus and epilepsy. Ataxia develops as does myopathy. Study reveals ragged red fibers in mitochondrial cells.

Answer 19

MERRF - Myoclonic epilepsy

Ragged red fibers - mitochondrial myopathy

Question 20

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?

Answer 20

“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

Question 21

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?

Answer 21

Corticosteroids

Question 22

Presentation consistent with inflammatory myopathy process.

Complaints of muscle pain/problems. What toxin/drug is likely causative agent?

Answer 22

Statins

Question 23

Patient presents with rhabdomyolysis - muscle necrosis and inflammation; denervation is also present. What drug/toxin is the likely causitive agent?

Answer 23

Ethanol

Question 24

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.

Answer 24

Polymyositis

- Inflammatory -

Question 25

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.

Answer 25

Dermatomyositis

- Inflammatory -

Question 26

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

Answer 26

Inclusion Body Myositis

- Inflammatory -