INDEX

[Link] TOPIC
1. Neuromuscular Disorders

1.1 Motor Neuron Diseases

1.11 ALS - Intro, Symptoms, Causes, Diagnosis,
Treatment
1.12 TM - Intro, Symptoms, Causes, Diagnosis,
Treatment
1.13 Case Study

1.2 Myopathies
1.21 CCD - Intro, Symptoms, Causes, Treatment
1.22 Polymyositis - Intro, Symptoms, Causes,
Treatment
1.23 Case Study
 NEUROMUSCULAR DISORDERS

MOTOR NEURON DISEASES:

[Link] Lateral Sclerosis:

Amyotrophic lateral sclerosis known as ALS, is a
nervous system disease that affects nerve cells in the
brain and spinal cord.
Symptoms:
Symptoms of ALS vary from person to person.
Symptoms depend on which nerve cells are affected.
ALS generally begins with muscle weakness that spreads
and gets worse over time. Symptoms might include:

 Trouble walking or doing usual daily activities.

 Tripping and falling.
 Weakness in the legs, feet or ankles.
 Hand weakness or clumsiness.
 Slurred speech or trouble swallowing.
 Weakness associated with muscle cramps and
twitching in the arms, shoulders and tongue.
 Untimely crying, laughing or yawning.
 Thinking or behavioral changes.
Causes:
ALS affects the nerve cells that control voluntary
muscle movements such as walking and talking. These
nerve cells are called motor neurons.
When motor neurons are damaged, they stop sending
messages to the muscles. As a result, the muscles can’t
function.
For about 10% of people with ALS, a genetic cause
can be identified. For the rest, the cause is not known.

Diagnosis:
 Electromyogram (EMG).
 Nerve conduction study
 MRI
 Blood and urine tests
 Spinal tap, known as a lumbar puncture
 Nerve biopsy
 Muscle biopsy

Treatment:
Treatments can’t reverse the damage of ALS, but they
can slow the progression of symptoms.
Medications:
 Sodium phenylbutyrate-taurursodiol (Relyvrio).
 Edaravone (Radicava).
 Riluzole (Rilutek, Exservan, Tiglutik).
Therapies:
 Breathing care
 Occupational therapy.
 Physical therapy.
 Speech therapy
 Nutritional support
 Psychological and social support.
[Link] Myelitis:
Transverse myelitis (TM) is a rare neurological
condition caused by inflammation of your spinal cord. It
often results in sudden symptoms, such as muscle
weakness, pain and bladder dysfunction.

Symptoms:
There are several different groups of symptoms for TM,
including:
 Abnormal sensations.
 Pain.
 Bowel and bladder issues.
 Muscle and movement issues.
 Sexual dysfunction.
 Other symptoms.

Causes:
In the case of TM, the covering around the nerve cells
in your spinal cord is damaged due to inflammation.
There are several possible causes of inflammation that
lead to transverse myelitis. The causes can be grouped
into the following categories:
 Idiopathic (no known cause).
Inflammation from an infection.
Systemic inflammatory autoimmune diseases.
Central nervous system diseases.

Diagnosis:
 MRI (magnetic resonance imaging) of entire spine
 Brain MRI
 Spinal tap (lumbar puncture)
 Blood tests

Treatment:
 IV (intravenous) glucocorticoids
 Plasma exchange therapy (plasmapheresis)
 Intravenous immune globulin (IVIG)
 Medicines to suppress your immune system
 Management of urinary function
 Management of bowel function
 Sexual dysfunction treatments
 Managing muscle tightness (spasticity)
 Preventing skin breakdown and pressure injuries
(bedsores)
Case study:
INTRODUCTION
Motor neuron disease (MND) is a heterogenous
group of disorders those selectively affect upper or lower
motor neurons, or both. Sporadic amyotrophic lateral
sclerosis (ALS) accounts for approximately 80% of all
cases of acquired motor neuron disease, whereas the
remaining 20% of patients have either only lower motor
neuron signs or a familial form of ALS (FALS).
Early in ALS, individuals complain of dyspnea with
exertion and frequently sigh at rest. With disease
progression, dyspnea at rest, inability to sleep in a supine
position, sleep apnea, and morning headaches are
present.
I present a case report involving a farmer who visited
the emergency department due to dyspnea.
CASE REPORT
A previously healthy, 66-year-old male patient
presented to the emergency department (ED) for
evaluation of progressive dyspnea, which had begun 3
months prior to presentation.
His vital signs included a blood pressure of 143/73
mm Hg, heart rate of 84/min, respiratory rate of 18/min,
temperature of 36.4℃, and an oxygen saturation of 89%
measured by pulse oximeter.
Electrocardiography revealed right atrial enlargement
and left ventricular hypertrophy with sinus rhythm.
Despite oxygen treatment with an 8-liter oxygen mask
with reserved bag, the dyspnea became worse, and the
oxygen saturation dropped to 86% after 3 hours.
Computed tomography of the chest identified
bronchiectasis in right upper lung field associated with
bronchopneumonia.
A bedside echocardiogram revealed good left
ventricular function (ejection fraction 56%) and normal
heart size without wall motion abnormality nor valvular
problems.
 The patient reported a 10 kg weight loss over the last
year and had been bedridden for generalized weakness.
The dyspnea progressed to respiratory failure after 6
hours from the time of presentation in the emergency
department, and intubation was required.
Further investigations with nerve conduction study
and electromyography demonstrated widespread
denervation without any electrophysiologic abnormal
findings of peripheral neuropathy.
Finally, the patient was discharged with
tracheostomy and home ventilator after several weeks’
antibiotics treatment, and followed up via out-patient
department.
DISCUSSION
MND refers to a group of diseases that affect the cells
that control voluntary muscle activity
Currently, no cures exist for MND. The only drug that
affects the course of the disease is riluzole, which blocks
the effect of the neurotransmitter glutamate. Riluzole
generally extends the lifespan of an MND patient by a
few months. The lack of effective medications to slow
the progression of MND does not imply that patients
cannot be medically treated. Treatment focuses on the
relief of symptoms associated with the disease as this
case.

CONCLUSION:
Primary care physicians are often quick to conclude
that motor power has weakened due to aging, only after
usual history taking without cautious physical and
neurologic examination. However, physicians who
encounter patients with dyspnea in ED have to rule out
pulmonary and cardiac dysfunction above all.
MYOPATHIES:

1. Central Core Disease:

Central core disease is a disorder that affects muscles
used for movement (skeletal muscles). This condition
causes muscle weakness that ranges from barely
noticeable to very severe. The severity of muscle
weakness may differ even among affected members of
the same family.

Symptoms:
CCD causes poor muscle tone (hypotonia) and
persistent muscle weakness in infants. In rare cases,
toddlers with the disease fail to walk at all, but usually
they’re just late in reaching motor milestones.
Older children and adults typically experience mild
disabilities that worsen slowly with time, if at all.

Causes:
Mutations in the RYR1 gene cause central core
disease. The RYR1 gene provides instructions for
making a protein called ryanodine receptor 1. This
protein plays an essential role in skeletal muscles.
For the body to move normally, these muscles must
tense and relax in a coordinated way. Muscle
contractions are triggered by the flow of charged atoms
(ions) into muscle cells.
 The ryanodine receptor 1protein forms a channel that
releases calcium ions stored within muscle cells.
The resulting increase in calcium ion concentration
inside muscle cells stimulates muscle fibers to contract,
allowing the body to move.

Mutations in the RYR1 gene change the structure of

ryanodine receptor 1 and the calcium channel that it
forms. The abnormal calcium channel alters the normal
flow of stored calcium ions within muscle cells.
Specifically, calcium ions “leak” slowly but continually
through the abnormal channel or calcium ions cannot
pass through the channel when they are needed. This
disruption in calcium ion transport prevents muscles
from contracting normally, leading to the muscle
weakness characteristic of central core disease.
Treatment:

Currently there is no treatment or cure for central core

disease, but there are some important ways to manage the
condition.
 Physiotherapy
 Exercise
 Corrective surgery
[Link]:

Polymyositis is one of a group of rare diseases called

the inflammatory myopathies that involve chronic (long-
standing) muscle inflammation and weakness, and in
some cases, pain.

Symptoms:
 Muscle weakness
 Difficulty swallowing
 Muscle ache
 Fatigue
 Shortness of breath due to heart and lung
involvement.
 Patchy red or violet rash around the eyes
 Fever
 Weight loss

Causes:
The exact cause of polymyositis is unknown, but the
disease shares many characteristics with autoimmune
disorders, in which your immune system mistakenly
attacks your own body tissues.
Treatment:
[Link] is treated with high doses of
corticosteroids as a first course of treatment.
[Link] severe cases of polymyositis, the intravenous
infusion of immunoglobulins (IVIG) has been an
effective treatment.
[Link] therapy also is important in the treatment of
polymyositis.

Case Study:
INTRODUCTION
Skeletal muscle weakness and hypotonia are the main
symptoms of congenital myopathies. Small rod-like
inclusions in muscle fibers are distinctive features of
nemaline myopathy. Different genetic mutations can
cause nemaline myopathy. Here, I report a case of
nemaline myopathy in a 16-year-old girl diagnosed using
next-generation sequencing.

CASE REPORT
A 16-year-old girl presented in the clinic with her
parents complaining of a long-standing history of
weakness. She reported that she never had the ability to
run. She had difficulty in climbing stairs and in reaching
out for things.
 As her family was concerned, her parents sought
medical advice from the age she was 2 years old. At the
age of 14 years, she had second opinion evaluation after
which she was labeled as congenital myasthenia. She
was started on prednisone and acetylcholinesterase
inhibitor. She continued this regimen for more than a
year without noticeable benefit.
Echocardiography and pulmonary function tests were
normal. Nerve conduction evaluation for right upper and
lower extremities was normal, but electromyography
was myopathic.
Whole-exome sequencing for the patient and her
parents revealed a pathogenic homozygous splice
acceptor variant in NEB gene c.1999-2A>G. Both
parents were carriers of the same variant.
She was diagnosed with autosomal recessive
nemaline myopathy. The patient was advised to do
strengthening and range of motion exercises for the
proximal muscles with maintaining normal vitamin D
level. She will be followed up in clinic regularly.

DISCUSSION
Nemaline myopathy is a type of congenital
myopathies characterized by varying degrees of
generalized body weakness and hypotonia with majority
of cases present at birth or early childhood, but sporadic
late-onset nemaline myopathy cases have been reported
in adults, which can be associated with HIV
 As Nemaline myopathy is a heterogenous disease
with more severe forms can cause dilated
cardiomyopathy and respiratory failure,
echocardiography and pulmonary function tests were
normal in the patient.

CONCLUSION
No specific treatment exists for nemaline myopathy
rather addressing symptomatic issues. Clinicians should
be aware of different phenotypes of neuromuscular
disorders and refer atypical cases to more specialized
centers.
BIBLIOGRAPHY:

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