5.

02 Muscular Disease and Muscular Dystrophies

Dr. Rene B Punsalan | March 12, 2019

SIGN Upper Motor Lower Motor Myopathic G
Neuron Neuron
I. MYOPATHIES
Atrophy None Severe Mild
A. Clinical Features
1. Muscle Weakness Fasciculations None Common None
B. Differential Diagnoses (! sign of
C. Diagnosis of Myopathy denervation)
D. Intermittent vs. Persistent Tone Spastic Decreased Normal/
II. INTERMITTEN MYOPATHIES Decreased
A. Myoglobinuria Distribution of Pyramidal/ Distal/ Proximal
B. Myotonia Weakness Regional Segmental
C. Hypokalemic Periodic Paralysis Tendon Hyperactive Hypoactive/ Normal/
D. Hyperkalemic Period Paralysis reflexes Absent Hypoactive
E. Paramyotonia Congenita Babinski Sign Present Absent Absent
F. Diagnostic Evaluation of Intermittent Weakness Take note: G
G. Metabolism of Muscle Contraction • Upper Motor Neuron:
1. Disorders of Glycolysis o Minimal atrophy (disuse atrophy)
2. Disorders of Fatty Acid Metabolism o Hyperreflexia
III. PERSISTENT MYOPATHIES
§ Motor units is released from suprasegmental inhibition
A. Inflammatory Myopathies
B. Dermatomyositis
o Distribution of weakness: Pyramidal/ Regional
C. Inclusion Body Myositis § Follows pyramidal tract (i.e. hemiparesis) thus,
IV. MUSCULAR DYSTOPHRIES unilateral
A. Duchenne’s Muscular Dystrophy o Spastic tone, Babinski sign, no fasciculations
B. Becker’s Muscular Dystrophy • Lower Motor Neuron
C. Limb-Girdle Muscular Dystrophy o Severe atrophy,
D. Emery-Dreiffus Muscular Dystrophy § Atrophy is ALWAYS a sign of denervation
E. Dystrophin (denervation atrophy)
F. Steroid Myopathy o Hypoactive/ Absent reflexes
G. Statin Myalgia § Motor unit is interrupted
V. References o Distribution of weakness: Distal or segmental
VI. Quiz § Follows the nerve that’s why distal; something to do
No objectives were given for this lecture with the nutrition of the nerve
(This is doc Punsalan’s last lecture before he retires) § Follows dermatomal segments
§ i.e. neuropathy
Legend: o (+) Fasciculations
Supplementary Book § Sign of denervation; common
Audio Recording Emphasized Notes o Decreased tone
Information
§ Because of interrupted reflex arc
& ! G • Myopathic
o Mild Atrophy
§ The muscle is involved but severity is more than the
I. MYOPATHIES UMN and less than LMN.
& Skeletal muscle diseases or myopathies are disorders with o Distribution of weakness: Proximal
structural changes or functional impairment of muscle. • Myopathic weakness is produced by a decrease in the
& These conditions can be differentiated from other diseases of number or contractile force of muscle fibers activated within
the motor unit (e.g., lower motor neuron or neuromuscular motor units.
junction pathologies) by characteristic clinical laboratory o With muscular dystrophies, inflammatory myopathies, or
findings. myopathies with muscle fiber necrosis, the number of
muscle fibers is reduced within many motor units.
A. Clinical Features o Motor unit= single motor neuron + several muscle fibers
• Proximal limb weakness (arms or legs) • On EMG, the size of each motor unit action potential is
• Symmetric decreased, and motor units must be recruited more rapidly
• Intact deep tendon reflexes (DTRs) than normal to produce the desired power.
o No interruption of motor unit as illustrated in the reflex arc o Because the muscle is affected, the size of the MUAP is
• Preserved sensation small.
o If associated with sensory loss, suggests injury to • Some myopathies produce weakness through loss of
peripheral nerve or CNS rather than myopathy. contractile force of muscle fibers or through relatively
• No Mental status changes selective involvement of type II (fast) fibers.
& However, asymmetric and predominantly distal weakness o These myopathies may not affect the size of individual
can be seen in some myopathies. An associated sensory motor unit action potentials and are detected by a
loss suggests injury to a peripheral nerve or the central discrepancy between the electrical activity and force of a
nervous system (CNS) rather than myopathy. muscle.
& On occasion, disorders affecting the motor nerve cell o Sometimes the pathology will just involve a selected group
bodies in the spinal cord (anterior horn cell disease), the of fibers such as the type II fibers and the EMG will be
neuromuscular junction, or peripheral nerves can mimic normal because it won’t be detected. Example of this is
findings of myopathy. steroid myopathy
o Electrical activity is normal as seen in the EMG but the
1. Muscle Weakness force of the muscle is decreased.
Table 1. Signs that distinguish the Origin of Weakness. (Doc’s ppt)
Review the differences between UMN and LMN weakness.

TRANSCRIBERS EDITOR Bermejo of
Padua, Palabrica, Palanas, Palima, (messenger)
1 10
Panopio

NOTES: (Chapter 22, Harrison’s Principle of Internal Medicine)
Doc marked this part of the chapter*

“Myopathic weakness is produced by a decrease in the

number or contractile force of muscle fibers activated within
motor units. With muscular dystrophies, inflammatory
myopathies, or myopathies with muscle fiber necrosis, the number
of muscle fibers is reduced within many motor units. On EMG, the
size of each motor unit action potential is decreased, and motor
units must be recruited more rapidly than normal to produce the
desired power. Some myopathies produce weakness through
loss of contractile force of muscle fibers or through relatively
selective involvement of type II (fast) fibers. These myopathies
may not affect the size of individual motor unit action potentials
and are detected by a discrepancy between the electrical activity
and force of a muscle.”
! One motor unit supplies several muscles, Myopathic
Figure 1. Gower’s sign. Inability to get up from the floor without
weakness results in decrease in the number of motor unit climbing up the extremities; there’s weakness of hip, thigh and trunk
th
or decrease in the force of each muscle fiber muscles. (Harrison’s 18 ed/ PPT).
! Exam Question: In muscle dystrophies, what is the
mechanism for the myopathic weakness? Answer: Decrease B. Differential Diagnosis
in the number of muscle fibers
! For it to be considered as differential diagnosis, it should
manifest affectation of motor function only.
For second bold texts* 1. Anterior horn cell disorder
! Selective weakness of the type II (fast) fibers is characteristic
• Purely motor
of Steroid Myopathy. This type of myopathy does not involve
• Anterior horn cell includes anterior root
the size of the mscles and therefore, the EMG is normal, but • E.g. Polio
there is a discrepancy between the electrical activity and
force of the muscle 2. Peripheral Neuropathy (Motor)
G FORCE IS WEAK; ELECTRICAL ACTIVITY IS NORMAL • The nerve is both sensory and motor. For it to mimic myopathic,
it should be purely motor.
• If it involves sensory, it is not considered as myopathic.
Table 2. Observations on Examination that Disclose Muscle • E.g. Guillain Barré
th
Weakness. (Harrison’s 19 ) G Doc will get 1 question from this
table. 3. Neuromuscular junction disorder
Functional Impairment Muscle Weakness
• Purely motor
Inability to forcibly close eyes Upper facial muscles
• Intermittent weakness
Impaired pucker Lower facial muscles
• E.g. Myasthenia Gravis
Inability to raise head from prone Neck extensor muscles
Inability to raise head from Neck flexor muscles
C. Diagnosis of Myopathy
supine
Inability to raise arms above the Proximal arm muscles (may be
1. Clinical Features (2019B)
head only scapular stabilizing • Most myopathies present with proximal, symmetric limb
muscles) weakness (arms or legs) with preserved reflex and sensation
Inability to walk without Knee extensor muscles • Asymmetric and predominantly distal weakness can be seen in
hyperextending knee (back- some myopathies
kneeing or genu recurvatum) • An associated sensory loss suggests injury to a peripheral
Inability to walk with heels Shortening of Achilles tendon nerve or the central nervous system rather than myopathy
touching the floor (toe walking) • On occasion, disorders affecting the motor nerve cell bodies in
Inability to lift foot while walking Anterior compartment of leg the spinal cord (anterior horn cell disease), the neuromuscular
(Steppage gait or footdrop)
junction, or peripheral nerves can mimic findings of myopathy
Inability to walk without waddling Hip muscles
gait
2. Electromyography (EMG)
Inability to get up from the Hip, thigh and trunk muscles
floor without climbing up the • Main function: differentiate myopathy vs neuropathy !
extremities (Gowers’ sign) • Upper motor neuron: normal EMG !
Inability to get up from a chair Hip muscles • If EMG (-): supports diagnosis of UMN
without using arms • Most important test that will confirm myopathy (2019B)
Another sign of weakness is walking on their toes due to shortening of • For certain types of myopathy like steroid, your EMG can be
Achilles’ Tendon normal (2019B)
• The needle EMG may reveal irritability on needle placement
suggestive of a necrotizing myopathy (inflammatory
myopathies, dystrophies, toxic myopathies, myotonic
myopathies), whereas a lack of irritability is characteristic of
long-standing myopathic disorders (muscular dystrophies,
endocrine myopathies, disuse atrophy, and many of the
metabolic myopathies) (2019B)

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• In addition, the EMG may demonstrate myotonic discharges • Thyroid function tests (e.g. thyrotoxic myopathy and/or
that will narrow the differential diagnosis (2019B) thyrotoxic periodic paralysis): there are myopathies related to
• Another important EMG finding is the presence of short- endocrine dysfunction !
duration, small-amplitude, polyphasic motor unit action
potentials (MUAPs) (2019B) II. TWO TYPES OF WEAKNESSES
• Such MUAPs can be seen in both myopathic and neuropathic Intermittent vs. Persistent
disroders; however, the recruitment or firing pattern is different • Two algorithms as your approach to suspected myopathy
(2019B) (2019B)
• In myopathies, the MUAPs fire early but at a normal rate to • When you are analyzing myopathic weakness, the first thing
compensate for the loss of individual muscle fibers, whereas in you would like to decide on is if you are dealing with intermittent
neurogenic disorders the MUAPs fire faster (2019B) weakness or persistent weakness (2019B)
• EMG can also be invaluable in helping to choose an • Intermittent – on and off; paiba-iba !; patient may be
appropriately affected muscle to sample for biopsy (2019B) completely normal at the time of examination (2019B) (e.g.
Myasthenia Gravis)
• Persistent
! Question to distinguish between the two, “Does the patient
have Myoglobinuria?
III. INTERMITTENT MYOPATHIES
Master the algorithms as this is where doc will get exam questions
from !

Figure 3. Diagnostic evaluation of intermittent weakness. AChR AB,

Figure 2. Activity recorded during EMG. A. Spontaneous fibrillation
acetylcholine receptor antibody; CPT, carnitine palmitoyltransferase;
potentials and positive sharp waves (both neuropathy and myopathy) B.
EOMs, extraocular muscles; MG, myasthenia gravis; PP, periodic
Complex repetitive discharges recorded in partially denervated muscle at
paralysis. Please refer to Appendix for Clearer Picture
rest C. Normal triphasic motor unit action potential (Look at C, as this is
the normal motor unit action potential – triphasic) D. Small, short-
duration, polyphasic motor unit action potential such as is commonly A. Myoglobinuria
encountered in myopathic disorders E. Long-duration polyphasic motor • Reddish/ Light brown to dark brown urine
unit action potential such as may be seen in neuropathic disorders. • First decision point in the algorithm (2019B)
• If there is no myoglobinuria, possible causes of intermittent
3. Muscle Enzymes paralysis include: (2019B)
• Elevated muscle enzymes are supportive of a myopathy ! o Myasthenia Gravis
• Elevated in a lot of muscle diseases, especially the o Periodic paralyses
inflammatory myopathies and even in muscular dystrophies § Hypokalemic
(2019B) § Hyperkalemic
• Creatine kinase (CK) is the preferred muscle enzyme to § Paramyotonia Congenita
measure in the evaluation of myopathies (2019B) • If there is myoglobinuria, possible causes of intermittent
• Damage to muscle causes the CK to leak from the muscle fiber paralysis include: (2019B)
to the serum (2019B) o Metabolic energy deficiencies
• Serum CK can be elevated in normal individuals without § Glycolysis
provocation, presumably on a genetic basis or after strenuous § Fatty acid utilization
activity, minor trauma (including the EMB needle), a prolonged
muscle cramp, or a generalized seizure (2019B) B. Myotonia
• Delayed/ Prolonged muscle contraction and slow relaxation
4. Muscle Biopsy • Difficulty in releasing objects after a firm grasp
• Ultimate source of diagnosis ! • If there is no myotonia, confirm with low potassium level during
the attack, then diagnosis is hypokalemic periodic paralysis.
• Final arbiter; cornerstone of diagnosis (2019B)
DNA test confirms diagnosis !
• An important step in establishing the diagnosis of a suspected
• If there is myotonia, diagnosis may be hyperkalemic periodic
myopathy (2019B)
paralysis or paramyotonia congenital !
• Usually obtained from a quadriceps or biceps brachii muscle,
• Elicit by holding a fist forcefully, then release suddenly.
less commonly from a deltoid muscle (2019B)
o In patients with myotonia, they have difficulty in relaxation
5. Other Tests
• Potassium and Thyroid tests
• Hypokalemic and hyperkalemic periodic paralysis !

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C. Hypokalemic Periodic Paralysis GGG NOTES:!
• Onset in adolescence
POTENTIAL EXAM QUESTION
• Men more than women
Hypokalemia: (-) Myotonia
• Attacks provoked by meals high in CHO or Na
• May accompany rest following exercise Hyperkalemia: (+) Myotonia
• Ocular and bulbar muscles involvement less likely
F. Diagnostic Evaluation
• Respiratory muscles usually spared. Not Fatal !
Note: For the algorithm on Diagnostic evaluation of Intermittent
• May take 24 hours to resolve on itself.
Weakness please check the Appendix. IMPORTANT To read and
• DNA test confirms the diagnosis understand the Algorithms for they will come out on the exam.
! Those affected will start to feel weak and is presents as
proximal muscle weakness. Forearm Exercise Test
! By history you will have several episodes.
! Example given by Doc. A young muscular man after working ! Important component in the algorithm, this test will differentiate
very hard goes home, eats a large carbohydrate meal then a glycolytic defect to fatty acid metabolism defect.
sleeps. Upon waking up he feels weak and goes to hospital • Indwelling catheter at antecubital vein
after which he is found to be hypokalemic. • Blood sample extracted for lactic acid and ammonia for baseline
! Work-up for patients with Hypokalemic Periodic Paralysis is to • Patient closes an opens hand for 1 minute
make sure you rule out a potassium losing nephropathy • Blood samples taken again at 1, 2, 4, 6, 10 minutes
(rapid loss of potassium in the urine. The first thing to do is • Failure of lactic acid to rise indicates glycolytic pathway
measure urinary potassium excretion. defect
• Failure of ammonia to rise indicates myoadenylate
NOTES:! deaminase deficiency.
Several years ago, the department of clinical neurosciences at
G. Metabolism of Muscle Contraction
UERM (Dr. Carandang) developed an interest in Bangungut • Chemical energy for muscle contraction is provided by the
syndrome (Also known as sudden adult death syndrome). He hydrolysis of ATP to ADP
collected cases and had a theory on the possibility of defining • ATP is restored by phosphocreatine and ADP
the pathogenesis of Bangungut. The usual phenotype is • Rephosphorylation requires the availability of CHO, fatty acids
patients with hypokalemic periodic paralysis, so Bangungot and ketones
syndrome is part of the spectrum of Hypokalemic Periodic • Glycogen is the main source of energy in muscle. Other
Paralysis; except that it is so severe it causes ventricular sources are blood glucose and fatty acids.
• Glucose is utilized first; then fatty acids
fibrillation cardiac arrest and the patient expires. Most if not all
• Myophosphorylase is the enzyme that initiates metabolism of
patients who experience Bangungut do not survive, only those
glycogen
who had CPR done early have increased chances of survival. • Increase in blood lactate reflects anaerobic metabolism of
Even previously healthy individuals are at risk. The usual glucose.
finding upon autopsy is acute pancreatitis, but the cause is
still unknown. Disorders of Glycolysis
! Just know the diseases that fall under glycolysis
D. Hyperkalemic Periodic Paralysis • Symptoms are precipitated by high-intensity exercise
• Onset in 1st decade of life • Myophosphorylase deficiency (McArdle’s disease) – most
common
• Attacks last 30 minutes to 4 hours
• Often normokalemic during attacks • & caused by mutations in the PYGM gene leading to
myophosphorylase deficiency. Symptoms of muscle pain
• Attacks precipitated by potassium administration.
and stiffness usually begin in adolescence. With severe
& Attacks are precipitated by rest following exercise and fasting.
episodes myoglobinuria can occur.
& HyperKPP is caused by mutations of the voltage-gated sodium
channel SCN4A gene. Acetazolamide or dichlorphenamide • Phosphofructokinase deficiency
can reduce the frequency and severity of attacks. Mexiletine to • Phosphoglycerate kinase deficiency
be helpful in patients with significant clinical myotonia. • Lactate dehydrogenase deficiency
• Beta-enolase deficiency
E. Paramyotonia Congenita
• A Na+ channel disorder of muscle (like Hyperkalemic periodic Disorders of Fatty Acid Metabolism
paralysis) • Carnitine Palmitoyl transferase deficiency (CPT)
• Attack of weakness is either cold-induced or spontaneous & CPT2 deficiency is the most common recognizable
• Myotonia is the prominent feature; weakness is mild. cause of recurrent myoglobinuria. Onset is usually in the
• Myotonia worsens with activity, in contrast to classic teenage years or early twenties.
myotonia. • Muscle biopsy for diagnosis
! In classic myotonia you have a problem with the relaxation of & Serum CK levels and EMG findings are both usually
the muscle. With repeated activity the problem disappears. The normal between episodes. A normal rise of venous
difference is that in Paramyotonia, the myotonia will worsen lactate during forearm exercise distinguishes this
with activity. condition from glycolytic defects. Muscle biopsy does
& This is in contrast to classic myotonia in which exercise not show lipid accumulation and is usually normal between
alleviates the condition. attacks. The diagnosis requires direct measurement of
& Paramyotonia Congenita is inherited as an autosomal muscle CPT or genetic testing.
dominant condition; voltage-gated sodium channel
mutations are responsible, and thus this disorder is allelic with Carnitine
HyperKPP • Practically all of the body carnitine is stored in muscle
• Two main functions:

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o Transports long-chain fatty acyl-CoAs from the cytosol ! There are three inflammatory myopathies (emphasized by doc):
compartment of the muscle fiber into the mitochondria for o polymyositis - proximal > distal weakness
beta-oxidation. o dermatomyositis - proximal > distal weakness
o Preventing accumulation of acyl-CoAs in the mitochondria. o inclusion body myositis - proximal and distal weakness

Figure 4. Carnitine cycle.

Figure 6. Diagnostic Evaluation of Persistent Weakness (20th ed.)
Muscle Biopsy
• Light microscopy NOTES:
• Histochemistry
• Please focus on the diagrams of both Persistent and
• Immunochemistry – with a battery of antibodies Intermittent myopathies. Doc mentioned that we
• E/M should focus on these two for the exam
• Establishes diagnosis in many disorders • Persistent Myopathy diagrams of both 19th and 20th
edition of Harrisons were included both in the ppt and in
IV. PERSISTENT MYOPATHIES this trans (see appendix).
• The first thing that you have to look at when dealing with • Take note that there are very minimal differences between
myopathies is to look for the pattern of weakness on the two diagrams. Doc still used the diagram in the 19th
neurologic exam edition during the lecture
• If the pattern of weakness falls under persistent myopathies,
follow the diagram under persistent weakness
A. Inflammatory Myopathies
• Polymyositis (PM)
• Dermatomyositis (DM)
• Inclusion body myositis (IBM)
• Represents the largest group of acquired and potentially
treatable causes of skeletal muscle weakness
• Autoimmune (related to Rheumatoid Arthritis)
• Clinical Features:
o Prevalence: 1 in 100,000
o PM as a stand-alone is rare
o Presents as progressive proximal symmetrical weakness
except for IBM which may be asymmetric
o IBM: distal weakness may be affected fairly early
o Ocular muscles are spared but pharyngeal (difficult
swallowing) and neck muscles (head drop) often involved
Figure 5. Diagnostic Evaluation of Persistent Weakness (19th ed.) • Diagnosis:
See appendix for clearer picture. NOTE: IMPORTANT to study the o CK – markedly elevated (in active disease as much as 50-
Algorithms – Focused on Exams. fold)
! Take note that you could mistake Ptosis and EOM weakness as ! It can present as normal CK levels when not in the
symptoms similar to those in Myasthenia Gravis, however active disease
remember that in Persistent weakness myopathy, these o Muscle biopsy
symptoms are persistent (persistent ptosis or EOM weakness) ! Confirms the inflammatory nature of the disease
unlike in MG, where it would be present as intermittent ! PM and DM both responds to treatment while IBM is
! Under proximal > distal, toxic endocrine myopathies include the least responsive to steroids (has poor response to
o Steroid Myopathy treatment)
§ Chronic use of steroids
§ Selectively involes the type II muscle fibers Polymyositis
§ EMG would be normal because it just selectively
• The actual onset of Polymyositis (PM) is often not easily
involves the Type muscle fibers determined, and patients typically delay seeking medical advice
o Use of Statins for several weeks or even months. (This is in contrast to
§ Potent statin would include Rosuvastatin Dermatomositis (DM), in which the rash facilitates early
o Thyroid problems (Thyrotoxic periodic paralysis and recognition).
Thyrotoxic Myopathy)
• PM mimics many other myopathies and is a diagnosis of
! Dropped head would be due to the weakness of the extensor
exclusion. It is a subacute inflammatory myopathy affecting
muscle of the neck
adults, and rarely children, who do not have any of the
! Normal CK total does not rule out myopathy although CK
following:
elevation supports myopathy
o Rash

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o Involvement of extraocular and facial muscles • The weakness can be mild, moderate, or severe enough to lead
o Family history of a neuromuscular disease to quadriparesis
o History of exposure to myotoxic drugs or toxins • Muscle biopsy shows significant perivascular and perimysial
o Endocrinopathy inflammation 

o Neurogenic disease
o Muscular dystrophy
o Biochemical muscle disorder (deficiency of a muscle Inclusion Body Myositis
enzyme) or Inclusion Body Myositis (IBM) as excluded by • Most common of the inflammatory myopathies
muscle biopsy analysis • Common in patients ≥50 years of age
• Polymyositis is rarely diagnosed as solitary disease: more • Suspected only later when a patient with presumed PM does
commonly, polymyositis occurs in association with a systemic not respond to therapy
autoimmune or connective tissue disease or with a known viral • Weakness and atrophy of the distal muscles, especially foot
or bacterial infection. extensors and deep finger flexors
o On occasion, may be asymmetric in distribution
• Some patients present with falls because their knees collapse
due to early quadriceps weakness
• Dysphagia is common
• Sensory examination is normal
• Progression is slow but steady
• Pathognomonic pattern characteristic: atrophy and weakness of
the flexor forearm (e.g., wrist and finger flexors) and quadriceps
muscles that is often asymmetric.
• Dropped head syndrome - important diagnostically; indicative
of selective neck extensor muscle weakness

Treatment
• Glucocorticoids (first choice) – prednisolone or prednisone
• Other immunosuppressive drugs
o Azathioprine
o Methotrexate
o Mycophenolate
o Monoclonal antiCD-20 antibody (rituximab)
o Cyclosporine
o Cyclophosphamide
Figure 7. Features Associated with Inflammatory Myopathies. Not o Tacrolimus
included in the lecturer's PPT. Lifted from Harrisons.
• Immunomodulation – IVIg
NOTES:
Polymyelositis: Typical symmetric; proximal than distal
Dermatomyositosis: Typical symmetric; proximal than distal
Inclusion Body Myositosis: Proximal and Distal + involvement
of Quadriceps; may be asymmetric

PM & DM: responds to Steroids very well

IBM: Poorly responds to Steroids


V. MUSCULAR DYSTROPHIES
• A group of progressive hereditary degenerative diseases of
skeletal muscles
• Muscular dystrophies are characterized by progressive
skeletal muscle weakness, defects in muscle proteins, and
the death of muscle cells and tissue

Figure 8. Polymyositis. From the lecturer's powerpoint. Look at the

inflammatory cells surrounding the fibers

Dermatomyositis
• Presentation of muscle weakness is similar to that of
polymyositis, but the denominative feature is a rash.
! Dermatomyositis is polymyositis + rash
• Heliotrope rash – rash consist of a blue-purple discoloration on
the upper eyelids with edema 

• Gottron’s sign – flat red rash on the face and upper trunk and
erythema of the knuckles with a raised 
violaceous scaly Figure 9. Progressive Muscle Dystrophies. Figure shows comparison
eruption between normal muscle tissue and affected muscle tissue. (Left) Normal
• V-sign – erythematous rash on anterior chest muscle tissue. (Right) Tissue has become disorganized and the
• Shawl sign – rash on the back and shoulders 
 concentration of dystrophin (green) is greatly reduced.
• Rash may worsen after sun exposure

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Table 3. Progressive Muscular Dystrophies • The boys fall frequently and have difficulty keeping up with
Table 387-5 Progressive Muscular Dystrophies friends when playing
• By age 5 years, muscle weakness is obvious by muscle testing
Type Inheritanc Defective Onset Clinical Other Organ
• On getting up from the foot, the patient uses his hands to climb
e Gene/Protein Age Features Systems himself up (Gower’s Maneuver)
Involved • Loss of muscle strength is progressive, with predilection for
Duchenne's XR Dystrophin Before 5 Progressive Cardiomyopathy proximal limb muscles and the neck flexors
years weakness of
girdle muscles Mental
• Leg involvement more severe than arm
impairment • Progressive scoliosis often develops that may be associated
Unable to with pain. Chest deformity impairs pulmonary function
walk after age
12
• By age 16-18 years, patients are predisposed to serious
sometimes fatal pulmonary infections. Other causes of death
Progressive include aspiration of food and acute gastric dilation
kyphoscoliosi • Intellectual impairment in Duchenne dystrophy is common
s
• Impairment of intellectual function appears to be non-
Respiratory progressive and affects verbal ability more than performance
failure in 2d • Treatment: Glucocorticoids
or 3d decade
o Administered as Prednisone, 0.75 mg/kg/day, significantly
Becker's XR Dystrophin Early Progressive Cardiomyopathy
childhood weakness of slow progression of Duchenne dystrophy for up to 3 years
to adult girdle muscles
Becker Muscular Dystrophy
Able to walk
after age 15 • Less severe form of X-linked recessive muscular dystrophy
results from allelic defects of the same gene responsible for
Respiratory Duchenne dystrophy
failure may
develop by • The pattern of muscle wasting closely resembles that seen in
4th decade Duchenne
Limb-girdle AD/AR Several Early Slow ± • Proximal muscles, especially of the lower extremities, are
(Tables 387-6, childhood progressive Cardiomyopathy prominently involved
387-7) to early weakness of
adult shoulder and • Significant facial muscle weakness is not a feature
hip girdle • Hypertrophy of calves muscles is an early and prominent finding
muscles
• Most patients with Becker dystrophy first experience difficulties
Emery-Dreifuss XR/AD Emerin/Lamin Childhoo Elbow Cardiomyopathy between ages 5 and 15 years
s A/C d to adult contractures,
humeral and • Patients with Becker dystrophy walk beyond age 15, whereas
Nesprin-1, peroneal patients with Duchenne dystrophy are typically in a wheelchair
Nesprin 2, weakness by the age of 12
! “I only included the table for you to get dizzy but I will not be asking • Mental retardation may occur in Becker dystrophy, but it is not
questions from this as it would be unfair to you. What I would want as common as in Duchenne
you to know is the GENERAL APPROACH to muscle diseases” • Treatment: the use of glucocorticoids has not been adequately
(from ppt) studied in Becker dystrophy
! Precipitated by HIGH INTENSITY EXERCISE
! I will not ask any questions in this table. “I WiLl NOt aSk anY qUeSTionS iN Limb-Girdle Muscular Dystrophy
this tABLe”
• Both males and females are affected, with onset ranging from
late in the first decade to the fourth decade
• Dystrophin
o Dystrophin is a rod-shaped cytoplasmic protein and a vital • The LGMDs typically manifest with progressive weakness of
part of a protein complex that connects the cytoskeleton of a pelvic and shoulder girdle musculature
muscle fiber to the surrounding extracellular matrix through • Respiratory insufficiency from weakness of the diaphragm may
the cell membrane. occur, as may cardiomyopathy
o Dystrophin deficiency has been definitively established as • A systematic classification of LGMD is based on:
one of the root causes of the general class of myopathies o Autosomal dominant (LGMD1) inheritance
collectively referred to as muscular dystrophy o Autosomal recessive (LGMD2) inheritance
o Dystrophy is the degeneration of tissue (muscle disease) due
to disease or malnutrition, most likely due to heredity Emery-Dreifuss Muscular Dystrophy
• There are at least five genetically distinct forms of Emery-
NOTES: EXAM QUESTION Dreifuss muscular dystrophy (EDMD)
Which final diagnostic test is most useful in diseases associated • Emerin mutations are the most common cause of X-linked
EDMD, although mutations in FHL1 may also be associated
with Myoglobinuria? MUSCLE BIOPSY
with a similar phenotype, which is X-linked as well
• Mutations involving the gene for lamin A/C are the most
The following readings towards the end are not part of the lecture common cause of autosomal dominant EDMD (also known as
nor was asked to read about, included only for completion purposes. LGMD1B) and are also a common cause of hereditary
Types of Muscular Dystrophies & cardiomyopathy
Duchenne Muscular Dystrophy • Prominent contractures can be recognized in early childhood
and teenage years, often preceding muscle weakness
• X-linked recessive disorder, also called pseudohypertrophic
• The contractures persist throughout the course of the disease
muscular dystrophy
and are present at the elbows, ankles, and neck
• Deficiency of dystrophin
• Muscle weakness affects humeral and peroneal muscles at first
• Duchenne Distrophy is present at birth, but the disorder usually and later spreads to a limb-girdle distribution
becomes apparent between ages 3 and 5 years

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• The cardiomyopathy is potentially life threatening and may b. Knee extensor muscle weakness
result in sudden death c. Upper facial muscle weakness
• A spectrum of atrial rhythm and conduction defects includes d. None of the above
atrial fibrillation and paralysis and atrioventricular heart block
• Some patients have a dilated cardiomyopathy. Female carriers
of the X-linked variant may have cardiac manifestations that Answer key: B, B, C, B, A
become clinically significant
• Treatment:
o Supportive care should be offered for neuromuscular
disability, including ambulatory aids, if necessary
o Stretching of contractures is difficult
o Management of cardiomyopathy and arrhythmias (e.g.
early use of a defibrillator or cardiac pacemaker) may be
life saving

ADDITIONAL POINTS (EXAM QUESTIONS)

TOXIC and ENDOCRINE causes persistent weakness

TOXIC
• Steroid Myopathy (also related to Endocrine)
• Statins Myopathy- ROSUVASTATIN, ATORVASTATIN,
SIMVASTATIN
o Number 1 side effect: MYALGIA
o Elevation of CK follows Myalgia
o Solution: Find an alternative drug that lowers
cholesterol besides statins: Ezetimide

ENDOCRINE
• HYPERTHYROIDISM/ THYROTOXICOSIS
o Cause both Toxic periodic paralysis (TPP) associated
with hypokalemia
o TPP is an intermittent weakness like HypoPP
o Why you always do Thyroid Function Tests
o Treatment: treat the Thyrotoxicosis

REFERENCES
1. Lecture Notes
2. Lecture Recording
3. Powerpoint “Muscle Diseases” by Dr. Punsalan
4. Harrisons 19e Chapter 462e; Harrisons 20e Chapter 441

QUIZ (S****ex 2019)

1. All of the following characterize myopathies except:
a. Proximal muscle weakness
b. Dull sensory loss
c. Intact DTRs
d. Symmetric involvment
2. Fasciculations are common in:
a. Upper motor neuron lesions
b. Lower motor neuron lesions
c. Myopathic
d. All of the above
3. In steroid myopathies where type II muscle fibers are
selectively affected the motor neuron action potentials
are:
a. Increased
b. Decreased
c. Normal
d. All of the above
4. Inability to pucker is indicative of weakness of the:
a. Upper facial muscles
b. Lower facial muscles
c. Neck extensor muscles
d. Neck flexor muscles
5. The Gower sign or the patient climbing up on his thighs while
rising from a sitting position is symptomatic of:
a. Proximal muscle weakness

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APPENDIX

Figure 10. Diagnostic Evaluation of Intermittent weakness. Take from Harrison’s 20th edition Chapter 441, pg. 3241. IMPORTANT to study
the Algorithms – Focused on Exams.

Figure 11. Diagnostic Evaluation of Persistent weakness. Take from Harrison’s 19th edition Chapter 462e, IMPORTANT to study the
Algorithms – Focused on Exams.

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Table 4. Progressive Muscular Dystrophies. For completion, Dr. Punsalan will NOT take any questions from this. NO NEED to memorize
this. Just read for your knowledge.

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