Neuromuscular Diseases

Question 1

List five potential causes of upper motor neuron dysfunction.

Answer 1

Intracranial hemorrhage, stroke, CNS trauma, CNS tumor, and transverse myelitis.

Question 2

Where are upper motor neuron lesions located anatomically?

Answer 2

Upper motor neuron lesions may include axons in the brain, through the spinal cord, and up to (but not including) the anterior horn cell.

Question 3

Where are lower motor neuron lesions located anatomically?

Answer 3

Lower motor neuron lesions may occur in the anterior horn cells, peripheral nerves, neuromuscular junctions, and/or muscles.

Question 4

A patient presents with weakness, muscle atrophy, fasciculations, fibrillations, hypotonia, and hyporeflexia. Does this patient have an upper or a lower motor neuron disorder?

Answer 4

Lower motor neuron

Question 5

List five potential causes of lower motor neuron dysfunction.

Answer 5

Infection, Guillain-Barre syndrome, botulism, myasthenia gravis, and rhabdomyolysis.

Question 6

What is the genetic inheritance pattern for spinal muscular atrophy?

Answer 6

It is an autosomal recessive disorder that maps to the SMN1 gene on chromosome 5q.

Question 7

What is the characteristic pattern of muscle involvement in patients with spinal muscular atrophy?

Answer 7

Muscle weakness is symmetric, with the proximal muscles affected to a greater degree. The legs are more commonly affected than the arms.

Question 8

Describe the typical presentation of spinal muscluar atrophy type 1.

Answer 8

This is the most severe form and presents at < 6 months of age with hypotonia and weakness, difficulty feeding, and tongue fasciculations. Most patients die by two years of age due to respiratory failure.

Question 9

What is Werdnig-Hoffman disease?

Answer 9

This is another name for spinal muscular atrophy type 1, AKA severe infantile SMA.

Question 10

Describe the typical presentation of spinal muscluar atrophy type 2.

Answer 10

Infants appear healthy at birth and achieve normal milestones, but then lose their milestones by 2 years of age. The majority die by 12 years of age. Weakness can be static for long periods of time and then progress with intercurrent illnesses.

Question 11

Describe the typical presentation of spinal muscluar atrophy type 3.

Answer 11

Patients present between 2 and 17 years of age with a progressive inability to walk or stand unaided. The degree of deficit correlates with the age of symptom onset - the earlier the onset, the greater the deficit.

Question 12

What is Kugelberg-Welander disease?

Answer 12

Spinal muscular atrophy type 3, AKA juvenile SMA.

Question 13

What is the inheritance pattern for Duchenne muscular dystrophy?

Answer 13

DMD is an X-linked recessive disorder, with up to 30% of cases being caused by spontaneous mutations.

Question 14

What gene and associated gene product are abnormal in patients with Duchenne muscular dystrophy?

Answer 14

DMD is caused by a mutation in the dystrophin gene and results in absent or deficient dystropin protein.

Question 15

What is a common presentation for a boy with Duchenne muscular dystrophy?

Answer 15

Boys present between 2 and 6 years of age with frequent falling, a waddling gait, and toe walking. Classic exam findings include: a child with calf muscle pseudohypertrophy and the Gowers sign (using arms to climb up the legs when rising from a seated position on the floor).

Question 16

What is the typical clinical progression for boys with Duchenne muscular dystrophy?

Answer 16

Affected boys usually lose the ability to walk by 12 years of age. Respiratory muscle weakness corresponds to gross motor weakness. Eventually, respiratory secretions can’t be handled and aspiration/infection commonly occurs. Cardiomyopathy is also a component of the disease. Respiratory failure is a common cause of death in these patients.

Question 17

How is Duchenne muscular dystrophy diagnosed?

Answer 17

If DMD is clinically suspected, measuring a CK is the next step and will be elevated in patients with the disease. Diagnosis is then confirmed by identifying a mutation of the DMD gene. Muscle biopsy is only used to confirm diagnosis in patients with negative genetic testing.

Question 18

How does Becker muscular dystrophy differ from Duchenne muscular dystrophy?

Answer 18

Becker resembles DMD but has a less severe course and later onset of symptoms. Diagnosis and management are the same as in DMD but Becker patients are able to retain ambulatory abilities after 15 years of age and life expectancy can be into the 4th or 5th decade.

Question 19

What is myasthenia gravis?

Answer 19

Myasthenia gravis is a disorder of neuromuscular transmission. In patients with the disease, the post synaptic acetylcholine receptors are reduced in number. This results in muscle weakness that worsens as the day goes on (and acetylcholine stores are depleted trying to overcome the decreased number of receptors).

Question 20

What is transient neonatal myasthenia gravis?

Answer 20

This disorder occurs when the newborn is exposed to transplacental passage of maternal acetylcholine receptor antibodies. The neonate presents within 72 hours of birth with hypotonia, weak cry, difficulty feeding, facial weakness, and ptosis. They eventually develop respiratory compromise as well, but the disorder resolves in 2-6 weeks as the maternal antibodies clear from the infant’s system.

Question 21

How does juvenile myasthenia gravis present?

Answer 21

The disease progresses gradually, with worsening muscle weakness, fatigability, and respiratory compromise. Muscle weakness is exacerbated by repetitive muscle use. Ocular muscles are involved, resulting in ptosis and ophthalmoplegia.

Question 22

How is myasthenia gravis diagnosed?

Answer 22

Diagnosis is made by demonstrating the presence of acetylcholine receptor antibodies (AChR-Ab) in the patient.

Question 23

How is myasthenia gravis treated?

Answer 23

Pyridostigmine (anticholinesterase - increases the concentration of acetylcholine at the receptor site). Most patients also require immunosuppression. Thymectomy induces remission in as many as 50-60% of patients. Plasmapheresis or IVIG may be utilized for short-term amelioration of worsening symptoms.

Question 24

How does Guillan-Barre syndrome classically present?

Answer 24

Look for a child with acute paralysis, beginning with weakness of the legs, followed by progressive paralysis that moves upward throughout the body. It can progress to involve the respiratory muscles and the cranial nerves. Tendon reflexes are absent. Sensory losses are rare and are restricted to the vibratory and position sense.

Question 25

What three infectious agents have been linked to the development of Guillain-Barre syndrome?

Answer 25

Campylobacter (up to 30% of cases), Mycoplasma, and EBV.

Question 26

How can Guillain-Barre syndrome and transverse myelitis be distinguished from each other?

Answer 26

Patients with transverse myelitis have both sensory and motor abnormalities below a defined spinal cord lesion. Patients with Guillain-Barre may have similar symptoms, including spinal shock, but will not have sensory involvement of the affected areas (excluding loss of vibratory and position senses).

Question 27

What is helpful about a lumbar puncture in Guillan-Barre syndrome?

Answer 27

Lumbar puncture can be helpful and frequently shows elevated protein levels as high as 100-150 mg/dL with a spinal WBC < 10 cells/µL (cytoalbuminologic dissociation).

Question 28

How is Guillain-Barre syndrome treated?

Answer 28

Treatment is supportive because the condition resolves over time, but close monitoring in an ICU is usually required for more severe disease due to the potential for respiratory compromise. Plasmapheresis and IVIG may improve recovery time, but steroids have not shown any benefit.

Question 29

What is Charcot-Marie-Tooth disease?

Answer 29

It is an inherited neuropathy that is caused by a variety of gene abnormalities that share a common clinical manifestation: symptoms typically present in the 1st or 2nd decade with progressive distal ascending weakness and associated loss of deep tendon reflexes and atrophy of the calf muscles.

Question 30

Why should honey be avoided in infants < 1 year of age?

Answer 30

Infants may contract botulism from spores present in honey.

Question 31

How do infants with botulism present?

Answer 31

Infants with botulism have constipation (usually the earliest symptom), generalized weakness, hypotonia, decreased ability to suck, poor gag reflexes, absence of deep tendon reflexes, facial diplegia, ptosis, and dry mouth.

Question 32

How is the diagnosis of botulism made in infants?

Answer 32

Look for the presence of C. botulinum spores in stool samples and confirm the diagnosis by confirming the presence of toxin in the stool.

Question 33

How do older children with botulism present?

Answer 33

Older children with botulism have dryness and soreness of the mouth, blurry vision, double vision, nausea, vomiting, anhidrosis (lack of sweating), ophthalmoplegia, and symmetrical facial, bulbar, and limb abnormalities.

Question 34

How are infants and children with botulism treated?

Answer 34

All affected patients should be admitted to the ICU to monitor for respiratory failure. Intubation is commonly required. Treat with antitoxin: equine serum botulism antitoxin may be used for patients > 1 year of age, and human-derived botulism immunoglobulin can be used for patients < 1 year of age.

Question 35

In what situation would antibiotic use be appropriate in the treatment of botulism?

Answer 35

Antibiotics are only recommended for treatment of wound infection in wound botulism after antitoxin has been administered.

Question 36

What is transverse myelitis?

Answer 36

Transverse myelitis refers to segmental spinal cord disease with both motor and sensory abnormalities at and below the level of the lesion. It usually occurs after viral infections, and lesions occur most commonly at the thoracic level.

Question 37

How is transverse myelitis diagnosed?

Answer 37

Diagnosis is made by demonstration of inflammation with MRI + contrast, which commonly shows intramedullary signal change (***include Image 12-11). Lumbar puncture may be performed after compressive etiology has been ruled out, but CSF is usually normal.

Question 38

How does multiple sclerosis present in childhood?

Answer 38

Symptoms are similar to those in adults: vision abnormalities, oculomotor disturbance, incoordination, and sensory deficits.

Question 39

What is multiple sclerosis?

Answer 39

MS is a multifocal demyelinating disease that is rare in childhood. It typically follows a relapsing-remitting course.

Question 40

How is multiple sclerosis diagnosed?

Answer 40

Patients must be found to have demyelinating lesions that are separated by both space and time. MRI is helpful and shows evidence of demyelination.

Question 41

A patient presents with weakness, hypertonia, clonus, spasticity, hyperreflexia, and a positive Babinski sign. The symptoms are affecting large muscle groups but there is only mild atrophy and an absence of fasciculations or fibrillations. Does this patient have an upper or a lower motor neuron disorder?

Answer 41

Upper motor neuron