1. Myopathies
Madison Pilato

2. Myopathy Case Congenital Myopathies Critical Illness Myopathy
Inflammatory Myopathies
References

3. Case
68 yo M w/o significant medical history p/w slowly progressive muscle weakness for 5 years.
First symptom R knee giving out on stairs
Today has difficulty rising from a chair and grasping with right hand
Exam: Intact CN, sensation and DTRs
RUE: 5/5 shoulder abduction, 5/5 elbow flexion and extension, 4/5 wrist flexion 5/5 wrist extension, 3-/5 finger flexion
LUE: 4+/5 finger flexion, rest is 5/5
RLE: 4+/5 knee extension, rest 5/5
LLE: 4+/5 hip flexion, 3+/5 knee extension, 4+/5 dorsiflexion
Case from Continuum, “Pattern Recognition Approach to Myopathy” Volume 12, Issue 3, p13-32

4. Congenital Myopathies

5. Core Myopathy Central core disease
Core Myopathy Central core disease
Clinical spectrum: apparent normalcy to severe weakness
Typically: hypotonia in infancy, developmental delay in childhood
Proximal limbs, axial muscles w/musculoskeletal abnormalities (hip dislocation, kyphoscoliosis, joint contractures)
Autosomal dominant
RYR1 mutation – majority of cases, rare resp weakness, rare cardiomyopathy. Malignant hyperthermia
SEPN1 severe respiratory weakness, severe scoliosis
Pathology:
Fibers w/regions devoid of oxidative enzyme activity
Predominance of type 1 muscle fibers
RYR1
Malignant hyperthermia

6. Nemaline (rod) myopathy “Nema”=thread
Nemaline (rod) myopathy “Nema”=thread
Variable presentation; genetically heterogeneous (AD, AR)
Infantile hypotonia: prominent facial and respiratory weakness (classic presentation), severe form with 20% mortality
Adult-onset: head-drop, dysphagia, respiratory insufficiency
Pattern of weakness: facial muscles, neck/trunk flexors, dorsiflexors, toe extensors
Earlier onset usually more severe. Less severe forms can stabilize or even improve
Pathology:
Rod shaped structures within muscle fibers
atrophic fibers without grouping
Trichrome stain: reddish purple thread-like inclusions within sarcoplasm
Type 1 fiber predominance
Ultrastuctural – intracytoplasmic rod-shaped structures

7. Centronuclear Myopathy Myotubular Myopathy
Clinically and genetically heterogeneous
Muscle fibers with large central nuclei that resemble myotubes (early fetal muscle fibers)
Severe, more common form is X linked. Occurs in male infants, marked hypotonia and weakness, respiratory muscle weakness and failure. Facial weakness and impaired bulbar function. Female carriers can have limb girdle or facial weakness. 1/3 die from respiratory complications in infancy
Less common form is AD or AR. Mild weakness and hypotonia may be unrecognized.
Pathology:
One or more centrally placed nuclei with surrounding clear area
Persistent fetal characteristics of muscle

8. Critical Illness Myopathy AKA acute quadriplegic myopathy
Steroids
Neuromuscular Blockade
Severe systemic illness
Critical Illness Myopathy AKA acute quadriplegic myopathy
Critically ill patient cannot be weaned off of ventilator, diffuse flaccid paralysis
2/3 conditions usually required: corticosteroid therapy, neuromuscular blockade, severe systemic illness (e.g., sepsis)
~25% of critically ill patients on MV longer than 1 week
Rapid onset, proximal weakness; may be asymmetric, may be muscle wasting
More common females
Resolves 3 weeks to one year; stop any offending agents
Pathology:
atrophy of muscle fibers (non-specific)
Electronic microscopic features are diagnostic/pathognomonic, selective loss of thick (myosin) filaments

9. Inflammatory Myopathies

10. Inclusion body myositis
Inclusion body myositis
Most common primary muscle disease over age 50; 3:1 male predominance
Slow symptom progression; asymmetric
Early involvement of quadriceps and ankle dorsiflexors; frequent falls
Early involvement wrist and finger flexor muscles
~50% swallowing difficulties; ~1/3 facial weakness
Muscle atrophy can be prominent
Can include peripheral polyneuropathy and sensory complaints
Poorly responsive to immunosuppressive tx, 50% WC bound after 10 years
Tx: supportive, exercise, supplement with creatine monohydrate
Pathology:
Intracytoplasmic vacuoles rimmed with granular material; inclusions react w/Abs associated with neurodegenerative diseases including beta-amyloid, tau, ubiquitin
Ultrastructual: diagnostic feature, inclusions w/in muscle cytoplasm, nuclei or both

11. Dermatomyositis = small vessel vasculitis
Proximal muscle weakness, weeks to months
Characteristic rash: red rash over eyelids and extremities (heliotrope, shawl, Gottrons)
Humorally mediated microangiopathy/vasculitis with ischemic necrosis of muscle fibers
Most common inflammatory myopathy of childhood, seen in all ages
3:2 female predominance
Frequency of cancer increased for 3 years after onset in adults
Tx: immunosuppressive
Pathology:
Inflammation of perimysial blood vessels
Lymphocytes plus plasma cells and eosinophils (mixed infiltrate)
Necrosis and phagocytosis in groups (microinfarcts)
Perifascicular atrophy = sublethal myofiber distal end of blood supply

13. Polymyositis Controversial; diagnosis of exclusion
Proximal muscle weakness over weeks to months with elevated CPK without skin changes of dermatomyositis. 2:1 female predominance
Oculobulbar rarely affected
May be associated with other autoimmune/collagen vascular diseases
Tx with immunosuppressive therapies (corticosteroids); 1/3 pts left with disability
Pathology:
Lymphocytic inflammation surrounding and invading otherwise healthy-appearing muscle fibers.
Rimmed vacuoles (IBM) and other types of inflammatory cells should be absent
CD-8 positive T cells, muscle fibers demonstrate upregulation MHC-I

14. References
Continuum, “Pattern Recognition Approach to Myopathy” Volume 12, Issue 3, p13-32
Prayson Neuropathology, 2nd Edition, Skeletal Muscle and Peripheral Nerve Disorders
Up to date: Congenital Myopathies
Up to date: Clinical manifestations of dermatomyositis and polymyositis in adults