Neuromuscular Disease Flashcards
Name 4 examples of myopathic muscular dystrophy.
- Duchenne
- Becker
- Myotonic
- Facioscapulohumeral
Describe the genetic basis, onset and clinical features of Duchenne’s muscular dystrophy.
- Mutation in dystrophin gene - Xp21
- X-linked recessive - affects many more men
- Onset age: 3-5
- Proximal weakness
- Lose ambulation (walking) in early teens
- Problems: scoliosis, respiratory failure, cardiomyopathy
- Death usually in 20s
Compare and contrast the genetics of Duchenne and Becker muscular dystrophy.
- Duchenne’s - frameshift deletion leads to non-functional protein (dystrophin)
- Becker’s - non-frameshift deletion leads to reduced function protein
Name the 2 licensed gene therapies for Duchenne’s muscular dystrophy.
- Ataluren - stop codon read through
- Eteplirsen - antisense oligonucleotide for a specific exon 51 mutation
Describe the inherited and acquired neuromuscular junction diseases.
Inherited:
- Congenital myasthenic syndromes
Acquired:
- Myasthenia gravis
- Botulism
Gower’s manouvre is often seen in which disease?
Duchenne muscular dystrophy
Describe the clinical features of neuromuscular junction disorders.
- Fatiguable weakness
- Usually proximal rather than distal
- Extraocular muscles and face often involved
- Reflexes - normal
- Sensory - normal
Describe the clinical features of neuropathy.
- Usually distal weakness but proximal if root or plexus damaged
- Early wasting
- Reflexes - reduced or absent
- Sensory/autonomic - can be involved - pain may occur
Describe the symptoms of ulnar nerve palsy.
- Affects all intrinsic hand muscles except LOAF
- Dorsal guttering
- “Ulnar claw”
- Lumbricals 3 and 4 (ulnar) weak whilst 1 and 2 (median) normal
Describe the pathological basis of myasthenia gravis and botulism.
Myasthenia gravis:
- Autoimmune response
- Antibodies attack nicotinic receptors
Botulism:
- Botulinum toxin prevents synaptic vesicles from fusing with membrane
- Reduced ACh release at NMJ
Describe the presentation of median, radial and common peroneal mononeuropathy.
- Median - carpal tunnel syndrome
- Radial - Saturday night palsy, “handcuff neuropathy”
- Common peroneal - foot drop
Name the most common acquired causes of polyneuropathy.
- Inflammatory - autoimmune, paraneoplastic
- Metabolic/endocrine - diabetes, renal failure, B12 deficiency
- Drugs
- Toxins - alcohol, lead
- Infection - HIV, leprosy
What is Charcot-Marie-Tooth Disease?
- Hereditary polyneuropathy
- Commonest genetic neurological disorder
- Prevalence: 1/2500
- 80 separate genetic diseases
- Presentation:
- Onset usually in childhood or teens
- Slowly progressing distal, symmetrical
- Distal wasting prominent
- Pes cavus - arched foot
- Pathology:
- CMT1 - demyelinating ~ 60%
- CMT2 - axonal ~ 30%
- ~ 10% mixed
What is Erb’s palsy?
- Upper trunk of brachial plexus - C5/C6 palsy
- Arm adducted - shoulder abductors weak - supraspinatus, deltoid
- Elbow extended - elbow flexors weak - biceps, brachioradialis
- Wrist pronated - supinators weak - biceps, supinator
- Wrist flexed - wrist extensors weak
What is radiculopathy?
Damage to nerve root - usually caused by prolapsed disc or arthritis
Causes radicular pain
If severe > weakness and wasting
