MEDINA, Miguel Andrei C.

2016-00448
Pedia Neuro Case #4
1. Give a 3-sentence summary of the pertinent features of the case. What other details in the
history and neurologic examination are lacking and must be elicited (if any)? Localize the lesion.
What neural structures are involved?
A 6-year old male grade 1 student, the first-born of a 24-year old mother, was brought to our
clinic with a chief complaint of difficulty in walking. On history, it was noted that one year prior to
consult he started complaining of easy fatigability, frequent tripping, and difficulty in climbing up
the stairs but it was reported that prior to this, there were no previous illnesses/hospitalizations
and the patient was born full term with no birth or maternal complications, despite the patient
being described as “lampa” as a young boy. Physical examination revealed lumbar lordosis,
prominent gastrocnemius muscles, mildly weak shoulder abduction, difficulty in standing from a
sitting position, tightness in the ankle joint, difficulty in foot dorsiflexion, hyporeflexia in the
triceps, biceps, and knee, and areflexia in the ankles, but with no joint contractures, sensorium
changes, cranial nerve deficits, sensory deficits, meningeal signs, or cerebellar signs, and with a
negative Babinski sign bilaterally.
With regards to the history, I would first clarify whether the onset of symptoms a year ago
happened suddenly or gradually, and whether these symptoms worsened or improved with time.
I will then point out the patient’s prominent gastrocnemius and lumbar lordosis and ask her to try
to recall when these first manifested in the patient, and whether they were already present when
the patient complained of his symptoms a year prior to consult. I will also ask the mother to
recall if the patient was doing anything special or out of the ordinary when the patient first
experienced his symptoms. I would also clarify whether the complaints of the patient come and
go (and its timing if this is the case), or whether it was present all throughout. I will also ask the
mother to specify what exactly she means by “lampa” and ask her to relay to me whether this
description was given by relatives or by medical professionals, and at what point in the history
this description was given. I will also ask the mother to relay if there were any medicines
given/things done to relieve or alleviate the patient’s symptoms and whether the patient’s
symptoms are affected by posture, rest, or hunger. I will also ask the mother if she thinks there
are any activities which seem to worsen the patient’s symptoms. I will also ask her to relay to
me the patient’s performance in school, specifically whether the patient has had difficulty coping
with either regular academic or PE classes and how he compares with peers. I will walk her
through the developmental milestones and help her remember if the patient has missed any. I
will ask for the patient’s vaccination record (check if polio vaccine has been given) and inquire
about social issues in the home (adequate nutrition for example). I will also question the mother
to ask them if anyone in their family had experienced similar symptoms, have developmental
disorders, or had other illnesses such as cancer. I will also ask if there are any associated
symptoms such as incontinence or pain. I will try to respectfully probe for consanguinity.
With regards to the physical examination, I would like to take the patients height to evaluate him
for stunting. I will also want to make a thorough examination of the patient’s skin to see if there
are any associated lesions. I would like to check the muscle tone of the extremities and check
for atrophy or fasciculations. I will also perform a more thorough evaluation of the patient’s
cerebellars if the patient is able: checking for dysarthria, dysmetria, dysdiadochokinesia, and
evaluating the patient’s gait.
The patient’s symptoms seem to be worse proximally rather than distally and is not associated
with sensory impairment. Assuming the deficits are symmetric and with associated atrophy of
the muscles, not episodic, and without fasciculations, then all these findings would point towards
a lesion in the muscles.
2. What is the etiology of the illness? What are the differential diagnoses?
The patient’s Hx and PE findings point toward a diagnosis of Duchenne Muscular Dystrophy
(DMD). The pseudohypertrophic gastrocnemius muscles, the patient’s proximal muscle
weakness manifesting first as pelvic girdle weakness (first manifested as difficulty climbing
stairs/frequent tripping), the difficulty standing from a sitting position (Gowers sign), the lumbar
lordosis, and the patient’s age and sex support this diagnosis.
An important differential is Becker’s muscular dystrophy (BMD) which has similar symptoms, as
it is also related to lack of dystrophin like in DMD. However, this is milder and usually has a later
onset. An intermediate phenotype in between DMD and BMD may also be seen.
Limb-girdle muscle dystrophy can also be another differential. This condition has a variable age
of onset from childhood to adulthood and presents with weakness of the proximal muscles in
both the upper and lower extremities. However, this condition is less prevalent than the
dystrophinopathies, and presents with less striking calf pseudohypertrophy.
Emery-Dreifuss muscular dystrophy presents with humeroperoneal muscle weakness and is
another differential. This condition however usually already presents with contractures and
cardiac disease so this is unlikely.
Spinal muscular atrophy is another possibility, because it also presents with proximal weakness
worse in the lower extremities, however this is accompanied with tongue atrophy and
fasiculations, diffuse areflexia/hyporeflexia, dysphagia, and respiratory insufficiency so this
diagnosis is unlikely.
3. Based on your main working diagnosis, what is the pathophysiology of the signs and
symptoms seen in this patient?
DMD is caused by a defective gene located on the X-chromosome which is needed for the
production of dystrophin, a protein found in muscle cells which is a critical part of the dystrophin-
glycoprotein complex (DGC). The DGC plays an important role as part of the structural unit of
muscle. Dystrophin normally stabilizes this glycoprotein complex and provides mechanical
support to the sarcolemma. In DMD, there is a total absence of dystrophin. Without dystrophin,
proteases may digest these complexes and initiate muscle degeneration, eventually leading to
muscle weakness, as experienced in our patient. The degeneration of muscles eventually leads
to the loss of reflexes and the development of joint contractures (currently, the patient is already
experiencing ankle joint tightness). Because dystrophin is also expressed in the heart and in the
CNS, cardiomyopathy and mental retardation may ensue in the future.
The majority of mutations causing dystrophinopathies such as DMD are caused by deletions of
one or more exons. This was found in about 60-65% of patients with DMD. The remainder were
caused by single nucleotide variants, deletions or insertions, or splice site variants. Some
patients present with symptoms characteristic of DMD but without an X-linked pattern of
inheritance; these are explained by mutations involving the glycoproteins associated with
dystrophin.
The pseudohypertrophy of the gastrocnemius muscles is caused by replacement of atrophied
muscle with fat cells or collagen and is seen only in patients with muscular dystrophy.
4. What laboratory examinations should be requested to help you come up with the correct
diagnosis?
A serum creatine kinase level should be taken to screen for DMD. An increased CK level is
compatible with the diagnosis and the child should then proceed to genetic testing. Analysis for
deletions/duplications and mutation scanning and sequence analysis to detect point mutations
are some of the techniques which can be used to clinch the diagnosis of DMD. Work-up such as
ECG can also be ordered to establish baseline cardiac function and to check for arrhythmias.
Likewise, vital capacity should be measured to establish baseline lung function. However, in this
case, there were no abnormal PE findings in the chest, so cardiorespiratory insults are unlikely
to be present at this point.
5. What are the initial approaches to therapy? What is the prognosis for this patient?
There is no medical cure for DMD. Treatment is supportive, to prevent contractures and to
manage cardiac and respiratory insults secondary to DMD. Glucocorticoids may be
administered to reduce the risk for scoliosis, and to delay the loss of ambulation. Physical
therapy (via passive stretching of the ankles, knees, and hips) may help prevent the risk of joint
contractures. Gentle exercise as tolerated should be prescribed to prevent muscle atrophy.
Continuous monitoring of cardiac and lung function should be done. Specifically, ECG and non-
invasive imaging of the heart should be done at least annually, increasing in frequency as
symptoms worsen. Serial monitoring of vital capacity should begin immediately. Once the
patient becomes non-ambulatory other parameters such as peak cough flow should also be
monitored.
The prognosis of this condition is poor. The mean age of wheel chair dependence in patients
with DMD is around 9.5 years, and patients eventually develop joint contractures, scoliosis,
worsening respiratory reserve, and sleep hypoventilation. The heart and CNS are also
eventually affected because dystrophin is also expressed here. Cardiomyopathy and
arrhythmias may develop. Unfortunately, the mean age of death for patients with Duchenne
muscular dystrophy is 25 to 30 years of age. Most patients die due to cardiorespiratory insults
secondary to the lack of dystrophin.
References
Robbins and Cotran Pathologic Basis of Disease Ninth Edition
Darras, B. T. (2020). Duchenne and Becker muscular dystrophy: Clinical features and
diagnosis. UpToDate. Retrieved from https://www.uptodate.com/contents/duchenne-and-
becker-muscular-dystrophy-clinical-features-and-diagnosis
Darras, B. T. (2020). Duchenne and Becker muscular dystrophy: Genetics and pathogenesis.
UpToDate. Retrieved from https://www.uptodate.com/contents/duchenne-and-becker-muscular-
dystrophy-genetics-and-pathogenesis
Darras, B. T. (n.d.). Duchenne and Becker muscular dystrophy: Management and prognosis.
UpToDate. Retrieved from https://www.uptodate.com/contents/duchenne-and-becker-muscular-
dystrophy-management-and-prognosis
Darras, B. T. (2018). Limb-girdle muscular dystrophy. UpToDate. Retrieved from
https://www.uptodate.com/contents/limb-girdle-muscular-dystrophy