Neuromuscular Problems ✅ Flashcards by Mollie O

What are neuromuscular disorders?

Condtions that lead to the impairment of muscle function

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What are the sites of pathology to consider in neuromuscualr disorders?

Anterior horn cells
Peripheral nerves
Neuromuscular junction
Muscle

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Where are nerve impulses generated?

Anterior horn cells

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What does the generation of nerve impulses in the anterior horn cells lead to?

Activation of muscle fibres

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What does anterior horn cell disease usually lead to?

Specific pattern of weakness

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What does the specific pattern of weakness produced by anterior horn cell disease depend on?

The affected part

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Why does the specific pattern of weakness produced by anterior horn cell disease depend on the affected part?

Because medial cells innervate proximal muscles, and lateral cells innervate more distal muscle groups

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What are the clinical features of anterior horn cell disruption?

Fasciculations
Lost reflexes
Fibrillation

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What are fasciculations?

Muscle twitches

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How does disruption of anterior horn cells produce fasciculations?

Disruption of anteior horn cells can lead to denervation, and the damaged alpha motor neurones produce spontaneous action potentials. These spikes cause the muscle fibres that are part of the neuron’s motor unit to fire, producing muscle twitches

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How is fibrillation detected?

Electrophysiological testing

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Why does disruption of anterior horn cells produce fibrillation?

As further generation occurs, only the remnants of the axon close to the muscle fibre remain. These individual axon fibres can generate spontaneous action potentials, whcih will only cause individual muscle fibres to contract, resulting in fibrillation

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Give 2 conditions that cause disruption of anterior horn cells

Spinal muscular atrophy

- Cervical cord damage

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What is the inheritence of spinal muscular atrophy?

Autosomal recessive

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What is the genetic abnormality in spinal muscular atrophy?

Defect in the SMN1 gene on chromosome 5

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What does the SMN1 gene encode?

The SMN protein

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What is the role of the SMN protein?

It is necessary for the survival of the motor neurons

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What happens when there is a deficit of SMN protein?

Death of neuronal cells in the anterior horn of the spinal cord occurs

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What muscles are most severely affected in SMA?

Trunk
Neck
Hip muscles

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Why are the trunk, neck, and hip muscles most severely affected in SMA?

Because they have the largest number of motor neurones, i.e. the biggest mass

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How can a diagnosis of SMA be made?

Testing for SMN1 gene deletion

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What is the most severe form of SMA?

Type 1

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What is type 1 SMA also known as?

Werdnig-Hoffman disease

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When does SMA type 1 present?

Infancy

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How does type 1 SMA present?

- Tongue fasciculations - Hypotonic - Areflexia - Early respiratory symptoms

What feature of type 1 SMA is almost pathognomic?

Tongue fasciculations

What is the prognosis of type 1 SMA?

Death within weeks or months

What is present at the same location as SMN1?

SMN2

What does SMN2 code for?

SMN protein

How many copies of SMN2 do most people have?

Why is SMN2 important in SMA?

In a child with SMA, the presence of normal copies of SMN2 can partially compensate for the absence of normal SMN1 function

What happens if a child with SMA has one or no copies of SMN2?

Their clincal course will be more severe

What investigation should be done if there is clinical suspicion of SMA?

Molecular genetic studies

What is the limitation of EMG and muscle biopsy in SMA?

Findings are non-specific

When does spinal muscular atrophy with respiratory distress (SMARD) present?

6 weeks - 6 months of life

What causes respiratory distress in SMARD?

Diaphragm weakness

What is the diagnostic test for SMARD?

Look for mutations in the IGHMBP2 gene

What is the inheritence pattern of SMARD?

Autosomal recessive

What radiological finding tends to be associated with SMARD?

Diaphragm eventration

Give 2 causes of cervical cord damage in neonates

- Congential malformation of cervical cord | - Injury during intrapartum period

What can cervical cord damage be difficult to differentiate from in the neonatal period?

Neonatal encephalopathy

What can be useful in distinguishing cervical cord damage from neonatal encephalopathy?

MRI of cervical cord and nerve routes

What is a key feature of disorders of the peripheral nerve?

Distal involvement, especially at the onset

Do peripheral nerve problems produce motor or sensory features?

May be both

Give an example of a peripheral nerve problem that produces motor and sensory features

Hereditary motor and sensory neuropathy (HMSN) type 1a

What is hereditary motor and sensory neuropathy (HMSN) type 1a also known as?

Charcot-Marie-Tooth syndrome

What causes Charcot-Marie-Tooth syndrome?

Gene mutations that cause defects in neuronal proteins

What do the defects in neuronal proteins affect in Charcot-Marie-Tooth syndrome?

Myelination of peripheral nerves

What is found on nerve conduction studies in Charcot-Marie-Tooth syndrome?

Reduced nerve conduction velocity

Give an example of a purely demyelinating disorder

Guillian-Barre syndrome

Which kind of neurones does Guillian-Barre syndrome affect most severely?

Motor fibres

Does Guillian-Barre syndrome affect pain and temperature sensation?

Little or no effect

Why does Guillian-Barre syndrome affect motor fibres much more than sensory?

Type I and II nerve fibres are myelinated, and have reasonably fast conduction velocity. Type III and IV fibres (responsible for pain and temperature) are lightly myelinated and unmyelinated respectively

What happens when a nerve impulse reaches the neuromuscualr junction?

It activates calcium channels

What is the result of activation of calcium channels at the neuromuscular junction?

Leads to regulation of acetylcholine

What does the regulation of acetylcholine at the neuromuscular junction lead to?

Muscle contraction via further post-synaptic action

What clinical features are present when acetylcholine is depeleted or it’s regulation is affected?

- Fatigability | - Diurnal variation

Give 2 conditions that affect the neuromuscular junction

- Congential myasthetic syndromes | - Myasthenia gravis

What can congenital myasthetic syndrome be divided into?

- Pre-synaptic - Synaptic - Post-synaptic

What is the genetic abnormality in most children with congenital myasthetic syndrome?

Gene mutations in one of the several genes encoding the acetylcholine receptors

What does a mutation in genes encoding the acetylcholine receptor lead to?

Deficiency at the endplate

What is the inheritence pattern of most genes causing congenital myathenic syndrome?

Autosomal recessive

What kind of mutation are most those causing congenital myasthetic syndrome?

Loss of function

What symptoms should prompt you to think of congenital myasthetic syndrome as a differential?

Infant presenting with; - Stridor - Respiratory difficulties, including apnoeas - Feeding difficulties - General hypotonia

How can congenital myasthetic syndrome be diagnosed?

- IV edrophonium (Tensilon) testing - Trial of pyridostigmine or neostigmine prior to a feed - Genetic testing - Stimulation single-fibre electromyography (StimSFEMG)

What is the limitation of IV edrophonium testing to diagnose myasthenia?

It can be difficult to interpret

How is a trial of pyridostigmine/neostigmine useful in diagnosing congenital myasthenic syndrome?

Can assess response

What needs to be assessed in the mother of a child with congenital myasthenic syndrome?

Evidence of maternal myasthenia

Where does genetic testing for congenital myasthenic syndrome need to be done?

A national myasthenia reference laboratory

How can StimSFEMG be helpful in diagnosing congenital myasthenic syndrome?

Can detect a decremental response following repetitive nerve stimualtion

Give 2 examples of neuromuscular disorders where the site of pathology is the muscle

- Congenital myotonic dystrophy | - Duchenne muscular dystrophy

What are the types of congenital myotonic dystrophy?

- Type 1 | - Type 2

What is type 1 congenital myotonic dystrophy also known as?

Steinert disease

How does type 1 congenital myotonic dystrophy differ from type 2?

Type 1 tends to present earlier and affected children can show signs from birth. Type 2 tends to be detected later and is a less severe form

What is the inheritence pattern of congenital myotonic dystrophy?

Autosomal dominant

What kind of genetic disorder is congenital myotonic dystrophy?

Trinucleotide repeat disorder

Where is the gene for myotonic dystrophy type 1?

Long arm of chromosome 19

What does the myotonic dystrophy type 1 gene mutation cause?

Expansion of the cytosine-thymine-guanine (CTG) triplet repeat in the DMPK gene

What does the DMPK gene code for?

Myotonic dystrophy protein kinase

How does the number of trinucleotide repeats affect the phenotype in myotonic dystrophy>?

The greater the number of trinucleotide repeats, the more severely affected the child will be

What should be done when a diagnosis of congenital myotonic dystrophy is suspected?

- Maternal examination - Electromyogram - Molecular genetic analysis for trinucleotide repeats

What is the most common muscular dystrophy?

Duchenne muscular dystrophy

When should DMD be suspected?

Any boy with delayed motor milestones

What can DMD be associated with?

- Learning difficulties - Disorders speech - Features of autistic spectrum disorder

What is a common examination finding in DMD?

Pseudohypertrophy of the calves

What is DMD caused by?

Mutation of the dystrophin gene

What is dystrophin?

An important structural protein within skeletal and cardiac muscle

Where is the dystrophin gene?

At locus Xp21

What is the inheritence of DMD?

X-linked recessive

Can girls be affected by DMD?

Yes, rarely

What shape is dystrophin?

Rod shaped

What is dystrophin bound to?

- One end to sarcolemma | - Other end bound to outermost actin filaments of the myofibril

What is the structural role of dystrophin?

Provides a cytoskeleton for the muscle fibre

What effect does the absence of dystrophin have on the muscle?

Allows excess calcium to penetrate the muscle cell membrane

What does penetration of calcium through the muscle cell membrane in DMD cause?

Alteration of signalling, leading to muscle degeneration and death

What is the first line investigation for DMD?

Blood creatinine kinase

What should be done if blood CK is raised in suspected DMD?

Genetic testing to identify specific exon mutation

How many exons is the muscle-specific form of the dystrophin gene formed of?

Is analysis able to identify the specific type of mutation in DMD?

Usually

What should be done if genetic testing is unable to find a mutation in suspected DMD?

Muscle biopsy

How can a muscle biopsy confirm a diagnosis of DMD?

Absence of dystrophin on staining

What other muscular dystrophy is caused by dystrophin gene mutations?

Becker muscular dystrophy

How does Becker muscular dystrophy compared to DMD?

It is milder