DISEASES OF THE MUSCLE

Gwenn F. Pabellano-Tiongson, MD, FPNA

Neurology – Neuromuscular and Electrodiagnostic Medicine
Assistant Professor 1
Department of Clinical Neurosciences
UERM College of Medicine
 LEARNING OBJECTIVES

• Provide a diagnostic approach based predominantly upon the

clinical history and neurologic examination.
• Identify whether myopathy is due to a defect in the muscle
channel, muscle structure, or a dysfunction in muscle
metabolism.
• Identify cause of myopathy
• Discuss pertinent laboratory testing that can be subsequently
used to confirm diagnosis
 CLASSIFICATION OF MYOPATHIES

ACQUIRED HEREDITARY
Drug-induced Channelopathies
Endocrine Congenital
Inflammatory/immune Metabolic
Myopathies associated Mitochondrial
with other systemic Muscular dystrophies
illness Myotonias
Toxic
 CLINICAL EVALUATION

“NEGATIVE” SYMPTOMS “POSITIVE” SYMPTOMS

Weakness Cramps
Exercise tolerance Contractures
Fatigue Muscle hypertrophy
Muscle atrophy Myalgias
Myoglobinuria
Stiffness
 TEMPORAL EVOLUTION

• Present at birth? Chidhood? Adulthood?

• Constant weakness: (Inflammatory, Dystrophies)
• Acute or subacute (Dermatoymyositis, Polymyositis)
• Chronic slow progression (Muscular dystrophy)
• Non-progressive (Congenital)
• Episodic weakness with normal strength interictally
(Metabolic myopathies, Periodic paralysis)
FAMILY HISTORY
 PRECIPITATING FACTORS THAT TRIGGER
EPISODIC WEAKNESS OR STIFFNESS

• History of medication?
• Provoked by exercise?
• Provoked by exercise or ingestion of carbohydrate
(Periodic paralysis)
• Cold exposure?
 ASSOCIATED SYSTEMIC SYMPTOMS OR SIGNS?

• Arrhythmias (Polymyositis, Dystrophies)

• Congestive heart failure (Metabolic, Dystrophies)
• Respiratory failure
• Hepatomegaly (Enzyme deficiencies in metabolic
myopathies)
• Rash (Dermatomyositis)
• Diffuse systemic disease (Endocrinopathy, infection,
Connective Tissue)
 LOCATION S/SXS
Facial Horizonal smile, inability to whistle
DISTRIBUTION OF WEAKNESS

Ocular Double vision, ptosis, disconjugate eye movements

Bulbar Nasal speech, weak cry, nasal regurgitation, dysphagia,
coughing during meals

Neck Poor head control

Trunk Scoliosis, lumbar lordosis, protruberant abdoment
Shoulder girdle Difficulty lifting objects overhead, scapular winging
Forearm/hand Weak grip, wrist drop
Pelvic girdle Difficulty climbing stairs, waddling gait, Gower’s
Leg/foot Foot drop, inability to walk on heels/toes
Respiratory Use of accessory muscles
 MANUAL MUSCLE TESTING

• 0-Complete paralysis
• 1-Minimal contraction
• 2-Active movement only with gravity eliminated
• 3-Full movement against gravity but cannot offer resistance
• to manual muscle opposition
• 4-Active movement against gravity and resistance but
• can be overcome by manual muscle opposition
• 5-Normal strength
 INSPECTION

• ATROPHY
• Proximal – Chronic myopathies
• Scapular winging – FSHD, LGMD
• Quadriceps and forearm flexors – Inclusion Body Myositis
• HYPERTROPHY
• Myotonia congenita
• Hyopothyroid myopathy
• Duchenne and Becker – “pseudohytrophy of calf”
 1. Proximal Limb Girdle weakness
2. Distal weakness
PATTERN RECOGNITION

• Inclusion body myositis, Myotonic Dystrophy

3. Proximal Arm/Distal leg Weakness
• Scapuloperoneal (FSHD)
4. Distal Arm/Proximal Leg Weakness
• Inclusion Body Myositis
5. Ptosis with or without Opthalmoparesis
• Myasthenia, Congenital Myopathies, Myotonic dystrophy
 6. Prominent Neck Extensor Weakness
• PM, DM, IBM, Myotonic Dystrophy
7. Bulbar Weakness
PATTERN RECOGNITION

8. Episodic Pain, Weakness and Myoglobinuria

• if with exercise: Metabolic
• If without exercise: Neuroleptic Malignant Syndrome,
Drugs, Infection
9. Episodic Weakness: Delayed or unrelated to exercise
• Periodic paralysis
10.Stiffness and Decreased Ability to Relax
• Myotonia, Channelopathies
 LABORATORY APPROACH

1. Creatine Kinase 3. EMG NCV

• High – Dystrophy, 4. BIOPSY
Inflammatory 5. MOLECULAR and GENETIC STUDIES
• Low – with profound 6. OTHERS:
muscle wasting, • Electrolytes, Thyroid function
corticosteroid admin, test, Immunologic markers,
Myoglobinuria
alcoholism,
• Forearm exercise testing
hyperthyroidism
2. Aldolase, SGOT, SGPT, LDH
 DEFINITION OF TERMS

• Myasthenic states: rapid

failure of contraction in the
affected muscles during
sustained or repetitive
activity.
• Contraction Myoedema:
stiffness and slowness of
contraction in a muscle such
as the quadriceps may be
seen on change in posture
CONTRACTION MYOEDEMA
 DEFINITION OF TERMS

• Rippling phenomenon:
after a period of relaxation,
stiffening and rippling
occurs in the contracting or PERCUSSION MYOTONIA
stretched muscles.

• Myotononia: a prolonged
failure of relaxation
following contraction of a
muscle is characteristic of
myotonia

MYOTONIA
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 TYPES OF MUSCLE DISEASES
HEREDITARY
Muscle Dystrophy
(Primary) Metabolic myopathes
• Glycogen Storage
• Myophosphorylase Deficiency
• Lipid
Congenital
Myotonias and channelopathies
Mitochondrial myopathies
ACQUIRED
Infectious myopathies
• Parasitic (Trichinosis, toxoplasmosis)
• Fungal
• Viral
Immune-Inflammatory myopathies
• Polymyositis
• Dermatomyositis
• Inclusion Body Myositis
• Necrotizing Myopathy
Endocrine myopathies
• Thyroid
• Corticosteroid and Cushing Disease
Drug-induced/Toxic
• Statins
• Alcohol
• High dose corticosteroids
INFLAMMATORY MYOPATHIES
 IMMUNE INFLAMMATORY MYOPATHIES:
POLYMYOSITIS, DERMATOMYOSITIS

• multisystem disorders with a wide variety of clinical

manifestations
• 20% have associated autoimmune or connective tissue
disease (eg. SLE, scleroderma, rheumatoid arthritis, PAN)
• Weakness develops subacutely, may be chronic or
present for many months
• Facial and EOMs are generally spared
• Malignancy linked most often with myositis are lung
and colon cancer in men and breast and ovarian
cancer in women
 POLYMYOSITIS

• subacute or chronic and symmetrical

weakness of proximal limb and trunk
muscles without dermatitis.
• insidious
• majority of patients are 30 to 60
years of age
• cardiac abnormalities
 DERMATOMYOSITIS

GOTTRON PAPULES
• patches of a scaly roughness over the extensor surfaces of joints (elbows,
knuckles, and knees) with varying degrees of pink-purple coloration.
HELIOTROPE
• Lilac-colored change in the skin over the eyelids, on the bridge of the nose, on the
cheeks, and over the forehead
V SIGN
• A predominance of rash over the neck and upper shoulders
SHAWL SIGN
• rash over the shoulders and upper arms, the shawl sign.
• distribution suggests that the skin changes reflect heightened photosensitivity
DERMATOMYOSITIS
 POLYMYOSITIS/DERMATOMYOSITIS:
TREATMENT

Treatment
a. Prednisone, 1 mkd
b. Immunosuppressant medications
c. IVIg
d. Plasmapheresis ineffective
 INCLUSION BODY MYOSITIS

• most common inflammatory myopathy in patients >50 years

• painless muscular weakness and modest atrophy, which is usually
distal in the arms and both proximal and distal in the legs.
• ~20% begins with focal weakness of the quadriceps, finger or wrist
flexors, or lower leg muscles on one or both sides
• Dyphagia is common
• Treatment: most interventions have demonstrated only limited
benefit.
MUSCULAR DYSTROPHY
 DYSTROPHINOPATHIES

• Inherited group of progressive myopathic disorders

resulting from defects in a number of genes required for
normal muscle function.
• Duchenne muscular dystrophy (DMD) is associated with
the most severe clinical symptoms
• Becker muscular dystrophy (BMD) has a similar
presentation to DMD, but typically has a later onset and a
milder clinical course
 DUCHENNE MUSCULAR DYSTROPHY

• Deletion or duplication at Xp21

• Abnormality of dystrophin (a cytoskeletal protein located in or
near the plasma membrane and seems to be associated with
membrane glycoproteins that link it to laminin on the external
surface of the muscle fiber; when dystrophin is absent, the
sarcolemma becomes unstable with subsequent excessive
influx of calcium due to damage, which causes muscle
necrosis
• X-linked recessive trait with females as carriers
 • Begins with difficulties walking and
running followed by difficulty
climbing and rising from chairs
(Gowers’ sign).
DUCHENNE MUSCULAR

• Calf hypertrophy
• Often have exaggerated lordosis to
DYSTROPHY

maintain upright posture.

• As disease progresses, arms and
hands affected with slight facial
weakness (but speech, swallowing,
and ocular muscles are spared).
• Iliotibial and heel cord contractures.
• By age 12 years, usually wheelchair
bound, by 20, usually respirator
dependent.
• Heart spared, but abnormal
electrocardiogram (ECG) (change in
RS amplitude
DMD: GOWER’S SIGN
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 MYOTONIC DYSTROPHY (STEINERT’S
DISEASE)

• Most common of all MDs (incidence =

13.5/100,000)
• AD with almost 100% penetrance
• Chromosome 19q13.2 (CTG repeat >40)
• Gene product—myotonin
 • Clinical
• Unlike any other form of major MD, it affects cranial muscles in
addition to those of the face (ptosis, occasionally extraocular muscles
are involved, dysphagia, dysarthria, temporalis muscle wasting)
MYOTONIC DYSTROPHY

• Pathognomonic: thin, narrow (hatchet) face; ptosis; thin/weak

sternocleidomastoid; and frontal balding
• Other signs and symptoms
• Weak voice due to involvement of laryngeal muscles.
• Affects distal > proximal muscles (with prominent finger flexor
weakness and footdrop with steppage gait).
• Mental retardation, cataracts, hypogonadism with testicular
atrophy (endocrinopathy).
• Cardiac arrhythmia or conduction abnormalities
• Myotonia (impaired relaxation of muscle contraction) causing
difficulty with shaking hands because letting go is difficult; may be
able to elicit percussion myotonia.
MYOTONIC DYSTROPHY
METABOLIC MYOPATHIES
 METABOLIC MYOPATHIES

• The symptoms, signs, and laboratory abnormalities resulting from a

metabolic myopathy vary with the underlying defect.
• Most patients with a metabolic myopathy (eg, glycogen storage
diseases, carnitine palmitoyltransferase deficiency) have dynamic
rather than static symptoms, and therefore usually complain of
exercise intolerance or muscle pain and cramps with exercise.
• increased risk for developing myoglobinuria and rhabdomyolysis.
APPROACH TO METABOLIC MYOPATHIES
 • Symptom assessment — When confronted with a patient with a possible
metabolic myopathy, the first step is to determine whether the symptoms are
dynamic, static, or both

1. Dynamic symptoms develop acute and recurrent episodes of reversible muscle

dysfunction related to exercise intolerance, prolonged fasting, exposure to cold,
APPROACH

general anesthesia, intercurrent infection, or low-carbohydrate, high-fat diet.

Some of these patients may develop myoglobinuria. In between episodes, the
patients are free of symptoms.
2. Static symptoms include proximal weakness, occasionally distal weakness,
generalized muscle weakness, and respiratory difficulties related to involvement
of respiratory muscles or fixed cardiomyopathy (as in acid maltase deficiency).
Other static features include progressive external ophthalmoplegia, peripheral
neuropathies, seizures, developmental delay, failure to thrive, short stature,
deafness, and ataxia. The symptoms themselves are not necessarily static since
progression of varying degree usually occurs depending upon the severity and
type of defect.
EVALUATION
ENDOCRINE MYOPATHY
 • Endocrine diseases are • Hypothyroidism
generally associated with
ENDOCRINE MYOPATHY

• Hyperthyroidism
hormonally mediated
systemic alterations in • Cushing syndrome
metabolism. • Adrenal insufficiency
• Muscle may become • Hyperaldosteronism
affected at any time • Hyperparathyroidism
during the course of
several • Diabetes
endocrinopathies.
 HYPOTHYROID MYOPATHY

1. Elevated serum creatine kinase

2. Myalgia
3. Muscle pseudohypertrophy - skin and subcutaneous tissues have a
thickened, doughy appearance. Serum muscle enzymes are usually elevated.
4. Proximal myopathy
5. Myoedema - small lump rising on the surface of a muscle when it is struck
with a percussion hammer, lasts for 30 to 60 sec, due to a sustained
contracture associated with delayed relaxation, because of slow
reaccumulation of calcium by the sarcoplasmic reticulum.
 MYOPATHY ASSOCIATED WITH CRITICAL
ILLNESS

• In the setting of critical illness, the most common causes of neuromuscular weakness are
critical illness myopathy (CIM), critical illness polyneuropathy (CIP), or a combination of the
two.
• Risk factors:
• Sepsis, multiorgan failure, and the systemic inflammatory response syndrome
• Use of intravenous glucocorticoids is another possible risk factor for CIM.
• Typical features:
• symmetric, flaccid limb weakness, which is usually worse in proximal compared with distal
muscles.
• extraocular muscles are relatively spared, and facial muscles are usually but not always
spared.
• Suspected in patients who develop flaccid muscle weakness and ventilatory failure after the
onset of critical illness. In the appropriate setting, the diagnosis is confirmed when other,
unrelated causes of weakness are excluded or deemed unlikely.
• Treatment: Directed toward aggressive management of medical conditions.
DRUG INDUCED MYOPATHY
 • Drug-induced myopathy may result from several different mechanisms
1. Direct myotoxicity
DRUG INDUCED MYOPATHY

• Examples include alcohol, cocaine, glucocorticoids, lipid-lowering

drugs, antimalarials (which are associated with vacuolar
myopathies), colchicine and zidovudine.
2. Immunologically induced inflammatory myopathy
• D-penicillamine, Statin-associated autoimmune myopathy
3. Indirect muscle damage
• Drug-induced coma with subsequent ischemic muscle compression,
drug-induced hypokalemia (eg, diuretics), drug-induced hyperkinetic
states (eg, delirium tremens or seizures secondary to alcohol), dystonic
states associated with phenothiazines, hyperthermia related to cocaine
use, and the neuroleptic malignant syndrome.
PERIODIC PARALYSIS
 PERIODIC PARALYSIS

• Periodic paralysis (PP) is a rare neuromuscular disorder related to a

defect in muscle ion channels, characterized by episodes of painless
muscle weakness, which may be precipitated by heavy exercise,
fasting, or high-carbohydrate meals.
• PP is classified as hypokalemic when episodes occur in association
with low potassium blood levels or as hyperkalemic when episodes
can be induced by elevated potassium.
• Most cases of PP are hereditary, usually with an autosomal dominant
inheritance pattern.
• Acquired cases of hypokalemic PP have been described in association
with hyperthyroidism.
 PERIODIC PARALYSIS

• Most of these diseases are caused by mutations in

genes that code for chloride, sodium, calcium, or
potassium ion channels in the muscle membrane,
and they are referred to as ion channel diseases,
or as "channelopathies"
• Within this group there are also instances of
muscle conditions that display no myotonia but
only periodic paralysis.
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