SANSONE

03/11/2020

The Adult Patient with Muscle Pain and Weakness

ADULT MUSCLE DISORDERS
Muscle diseases are rare diseases. However, we need to do this because you might encounter a
patient having muscle pain or feeling weak. You should be able to distinguish between CNS
weakness and PNS weakness. The muscle disorders could be different, from muscular
dystrophies to motor neuron diseases.

We’re going to focus on the most frequent ones out of the rare diseases. DM = myotonic
cystrophy affects 1 in 2500. It has a congenital form. Then comes ALS, FSHD (facial-scapular
humeral dystrophy), LGDM (limb girdle muscular dystrophies) and SMA.

They might be rare by themselves, but together they might be common.

The muscle diseases are diagnosed clinically. You should focus on the main site of onset of
weakness, and where it spreads in time. You have to figure out where this weakness is. If you
want to discriminate between proximal and distal, you’d have to ask questions. The proximal
would have difficulties getting up and sitting down.

Is it a weakness of power, or is it a fatigue-type weakness. Can they not sprint, or can they not
walk long distances due to muscle pain? The power problems are in the muscle fibres, whereas
the endurance problems are related to the mitochondria.

You have to ask about the muscle mass as well. It might not be that infrequent that you might
find reduced muscle bulk. If you see an increased muscle bulk, it may be to compensate the
reduced power of other districts.

Laboratory
You’d want to look at CK, LDH and aldolase. CK is usually below 200 units/L. They are enzymes
produced in the muscle, and there are isoforms in the cardiac muscle, used to test cardiac
infarct. There’s also a brain isoform. But, since most comes from the muscle, it is a measure of
muscle involvement, as it may rise even after a gym workout. If you fall and bruise your
muscles, getting a hematoma, your CK values might increase in the range of 1000s. The same is
for IM injections. Therefore, it is a non-specific test. You’d need to have 3 blood samples at
different times, with 2-3 days of rest (no exercise, no falling, no injections).

In the muscular dystrophy cases, the CK values may be as high as 10,000-20,000, whereas in an
inflammatory case, it may be around 30,000-50,000. So, if you see 300-400 (e.g. after gym
workout) is not indicative of muscular dystrophy. But, you’re not treating CKs, you’re treating
the patient, and don’t necessarily think that a rising CK is a worsening of the muscular
condition. However, it can be used to check the values to see response to treatment (e.g. use of
steroids for treating inflammatory disease).

This is relevant for surgery. Muscles are susceptible more than other places, especially in the
recovery phase of general anaesthesia. If you have a neuromuscular problem (e.g. endplate
problem in Myasthenia Gravis, where the ACh has antibodies against it), and you use drugs that
interfere with these receptors (e.g. anaesthesia) the patient might be in additional distress (e.g.
not be able to breath properly). Therefore, assess CK levels properly before surgery, and let the
surgeon know about your muscle problems.

Neurophysiology
This refers to the electromyography, needle exams? And…… You’d want to describe the size and
the duration of the muscle conduction.

Muscle Biopsy
Limited to cases where diagnosis is uncertain. You can look at the histology with different types
of stains, distinguishing between the Type I and Type II fibres, as well as their distribution and
size. You can see the mitochondria with Gomori staining, and the lipid droplets and glycogen
deposits by Oil Red and PAS, respectively.

Becker muscular dystrophy has decreased protein and the protein that is present is less
functional, whereas in the Duchenne muscular dystrophy, the protein is absent.

Molecular Diagnosis
There are different ways by which a muscle disease can be inherited. But you don’t need to
know the details. DMD affects not only the skeletal muscle, but also cardiac and respiratory
muscles. Cognitive function is also affected, as there is an isoform (?) of dystrophin in the brain
helping with cognition. Patients die with cardiac and respiratory arrest.

You make the diagnosis of DMD at 3-4 years of age, when the patients start walking on their toes
(as the Achilles tendon retracts). The boys start preferring to play if they are seated, they need
to use the arms to get up, or need help walking upstairs or downstairs. They may waddle when
running. The blood test in a paediatrician would show a CK value of around 10,000 which is
typical for this disease. They might break a bone when they fall, and in the tests, they might
show a high CK value. Nowadays, there are some treatments to treat DMD, although in the past,
nothing could be done.

Steroids are given, although inflammation is not involved, as steroids act as membrane
stabilizers, strengthening the muscle membrane, and the patients would worsen at a slower
rate.

Early introduction of inteventions for cardiac and respiratory problems, as well as the use of
steroids changed the prognosis of these diseases drastically. Nevertheless, the ambulation is still
lost in 14-15 years of age, and stay there, where they cling on to life with a respiratory support
and eat with a naso-gastric tube.

There are some treatments which target specific mutations. Translarna is one of the drugs used.

Becker Muscular Dystrophy

Dystrophin has a qualitative abnormality. It presents later on in life with respect to DMD,
starting at 16-18, and progresses slower.

FSHD  know that these patients exist, you don’t need to diagnose it. The face might seemingly
be totally normal. For this, you’d need to see the body as well (scapular retraction etc.) The
patient might have something known as “transverse smile”. Their eyes might not be closing
properly, due to the orbicularis oculi weakness. This is due to the facial muscles being affected
in this disease. This might also be seen in different muscles. For example, the trapezius muscles
are compensating for the weak deltoid muscle in the picture below.

In FSHD, lower limbs might also be present, where the patients tip over, due to the problems
related to the dorsiflexion. The disease is relatively slow, and there is the sparing of respiratory
and cardiac muscles.

LGMD
These patients refer to difficulty climbing stairs, or lifting their arms. There is a great genetic
heterogeneity, as it can be dominant or recessive.

Congenital Myopathies
Instead of dystrophy, myopathy is used here, where the muscle fibres themselves are
problematic and disruptive, but are not necessarily replaced by fat and other tissues.

Metabolic Myopathies
Seen when the lipid pathway is affected, and you’d have lipid build up in muscles.

Mitochondrial Myopathies
CPEO is quite typical of mitochondrial myopathies, where the patient complains of fatigue but
also has ptosis, and also difficulty to move the eyes, very often bilaterally.

Myoclonus epilepsy is also part of this group, where the patient jerks, but is cognitively aware.

E-depenone is used for Leber, which might cause blindness.

Inflammatory Myopathies
Polymyositis and Dermatomyositis have specific findings in biopsy, whether inside the cells or
perivascular.

Differential Diagnosis of Myotonias

You’d give the patient 2 fingers, and give them the opportunity to squeeze. Some patients will
not be able to let go, which will mean the patient has myotonia, and then you’d need to do other
tests to see what type of myotonia it could be. The subdivision that should be considered is
listed below. You look for myotonia electrically (and not be satisfied by the clinical myotonia).
Check if there is a warm up phenomenon (which will be in the dystrophic patient, and disappear
after 4-5 squeezes).

Percussion Myotonia  if you strike the hammer to the thenar eminence, you’ll see the dip, and
then the thumb would contract, and stay there. You can also do this on the arm, with the finger
extensors. Basically, if myotonia is not present, the fingers go down immediately, but if you have
myotonia, the finger lags before relaxing.

If you stick a needle in a normal muscle, you don’t record any activity. If you stick a needle in a
person with myotonia, you’ll have a discharge and you’ll hear a
wieeeeeeeewwwwwwwuuuuuuuiiiiiieeeeeeewwwwwww.

DM1 Phenotype
They may have some very mild phenotype, with some scapular retraction and minimal atropy
or hypertrophy, and nothing really changes in time. The patient, though, although might look
normal, can have difficulty getting up from a squat.

PAIN
Where the pain is, what are the triggers, is there myoglobinuria and does it give cramps.