Neurology - Diseases of muscles Flashcards
3 classes of muscle disease
- ) Neurogenic
- ) Myopathy
- ) Disorders of NMJ
What are neurogenic muscle diseases?
Muscles diseases caused by damage to muscle innervation
Can occur due to damage to UMNs (brainstem and spinal cord) or LMNs (nerve roots and peripheral nerves)
What is fibre type grouping?
Loss of normal mosaic arrangement of muscles fibres due to re-inervation by non damaged motor neurones
In certain long standing neurogenic muscle diseases - e.g. peripheral neuropathy - damage to motor neurones leads to neurogenic atrophy of all fibres innervated by that neurone
Atrophied fibres can be re-inervated by axons from other motor neurones supplying adjacent fibres - this changes the fibre type of muscle
Examples of neurogenic muscle diseases
- ) Motor neurone disease
- ) Spinal muscular atrophy
- ) Peripheral neuropathies
- ) Misc spinal disorders
Motor neurone disease
= Progressive degenerative disease affecting anterior horn cells in the spinal cord
This causes denervation atrophy and LMN signs (i.e. fasciculations and weakness)
What is spinal muscular atrophy and what gene is involved?
= common autosomal recessive disorder
It is caused by homozygous loss of the survivor motor neurone gene 1
Present in 4 main forms - types 1-3 all affect infants and children, while type 4 occurs in adults and has slower progression with variable disability
What misc spinal disorders can cause neurogenic muscle disease?
- Poliomyelitis
- Syringomyelia
- Degenerative diseases of the vertebral column (e.g. prolapsed disc, osteoarthritis)
All of these diseases affect the anterior horn cells or ventral nerve root
Name the 5 main types of myopathy
Myopathy - disease affecting muscles
- ) Muscular dystrophies
- ) Inflammatory myopathies
- ) Congenital myopathies
- ) Metabolic myopathies
- ) Toxic myopathies
Muscular dystrophy
= group of inherited disorders characterised by muscle fibre destruction
Muscle innervation is usually normal
Duchenne muscular dystrophy
X linked disorder affecting males
Caused by loss or reduction in the dystrophin gene product - protein normally present between muscle cell membrane and cytoplasm
Loss of dystrophin causes disruption of cell membrane and unregulated calcium influx - muscle damage
What is the usual presentation of Duchenne muscular dystrophy?
Normally presents between ages 2-4 years
Proximal muscle weakness + pseudo hypertrophy of the calves
Patients struggle to climb stairs, walking and rising from the floor (children with DMD will often use their hands to “climb up their legs” = Gower’s sign)
What enzyme is raised in DMD?
Serum creatinine phosphokinase (CPK) is raised in the early stages of the disease and in female carriers
Prognosis in DMD
Most patients die before aged 20 from cardiomyopathy (also occurs as part of the disease)
Why is DMD also called pseudo hypertrophic muscular dystrophy?
Based on biopsy findings of DMD:
- Irregular sized diameter muscle fibres
- Fibres showing hyaline degeneration with attempts at regeneration
- Muscle mass replaced by adipose and connective tissue which contributes to pseudo hypertrophy
Becker muscular dystrophy
Also an X linked disorder with similarities to Duchenne muscular dystrophy
But onset is later and progress is slower so many patients survive to adulthood
Allelic variant of DMD - involves deletions of p21 region on X chromosome
What is Limb-girdle dystrophy?
Also called Erb dystrophy
Rare autosomal recessive disorders
Usually present at 20-40 years with pelvic girdle weakness and later on shoulder girdle
Biopsy findings are similar to DMD
Fascioscapulohumeral dystrophy
= Rare autosomal dominant disease affecting both sexes equally
Usually presents in childhood with shoulder and facial weakness and characteristic scapular “winging”
Biopsy shows slowly progressive dystrophy with lymphocytic infiltration
What is myotonic dystrophy?
= Rare autosomal dominant condition caused by unstable CTG repeat in cAMP dependent protein kinase on chromosome 19
Presentation of myotonic dystrophy
Usually presents between 15-40 with weakness and wasting of facial, pelvic girdle and proximal limb muscles
Myotonia (persistence of muscle contraction after voluntary action has ceased) is common
Patients also exhibit other systemic disorders - e.g. cataract, gonadal atrophy, and diabetes
What agents can cause inflammatory myopathy?
Muscles can be involved in a number of infections
- Bacteria - e.g. clostridia, strep
- Viruses - e.g. coxsackie B
- Parasites - toxoplasma, trichinella
Polymyositis
= most common inflammatory disease affecting muscle
Most commonly occurs in adults - F>M
Associated with collagen vascular diseases (e.g. SLE) or cancer
Patients usually present with weakness, pain and swelling of proximal muscles
Dermatomyositis
= Microangiopathy affecting skin and muscle
Complement deposition causes capillary lysis and muscle ischaemia
Treatment of polymyositis and dermatomyositis
Muscle injury is caused by clonally expanded CD 8 T cells (biopsy shows lymphocyte and macrophage infiltrate)
Mechanism of antigen sensitivity is unknown
Treat with immunosuppressives (e.g. steroids, azathiaprine)
Inclusion body myositis
Type of inflammatory myopathy
Most common in elderly patients and resembles polymyositis but does not respond to steroids
Fibres show inflammation and fibrous necrosis with vacuoles and filamentous intracellular inclusion bodies
What are congenital myopathies?
These are very rare and occur as inherited disorders
Characterised by hypotonia and flaccidity at birth
Many prove fatal
Hypotonia is also associated with cerebral palsy, Downs syndrome and hypothyroidism
Metabolic myopathies
Muscles involvement occurs in a number of inherited metabolic disorders mostly with other systemic symptoms - e.g. stroke like symptoms and lactic acidosis in mitochondrial cytopathy
2 examples:
i) Malignant hyperthermia - autosomal dominant condition causes abnormal sensitivity to anaesthetic agents causing fatal hyperpyrexia on exposure
ii) Endocrine myopathies
What are the 2 patterns of myopathy caused by alcohol?
- ) Acute alcoholic myopathy - results from bouts of heavy drinking and causes acute fibre necrosis. Myoglobin released from muscles causes AKI
- ) Subacute alcoholic myopathy - occurs in chronic alcoholics. It causes proximal muscle weakness and atrophy with selective loss of type 2b fibres
Myasthenia gravis
Autoimmune disease affecting neuromuscular transmission
Number of post synaptic acetylcholine receptors is reduced and patients have high anti-AChR antibodies
What other condition is associated with myasthenia?
Thymoma (10% of patients)
Clinical presentation of myasthenia
Painless muscular weakness by repetitive or sustained contraction
Most commonly affecting face and eyes - bilateral ptosis and diplopia
Dysarthria and dysphagia can occur
Proximal muscles more affected than distal, and upper limbs more affected than lower
Examination findings in myasthenia
Weakness on sustained contraction is most common
There is no wasting or LMN signs and reflexes are intact
How is a patient with myasthenia diagnosed?
- Serum anti-AChR antibody titre
- Edrophonium (tennsilon test) = short acting acetylcholinesterase inhibitor produces temporary increase in synaptic ACh levels - rapid, transient improvement in clinical features
- EMG
- TFTs
- CT thorax - thymoma
What treatment options are available for MG?
- ) Long acting, oral anti cholinesterase - e.g. pyridostigmine or neostigmine
- ) Corticosteroids - alternate day regime should be started at a low dosage as there is a risk of increasing weakness in early stages
- ) Immunosuppression with azathioprine (useful as steroid sparing)
- ) Thymectomy at ANY age increases chance of remission
- ) Plasmapheresis - intractable cases
What antibiotics should be avoided in MG?
Certain antibiotics such as aminoglycosides can precipitate neuromuscular blockade especially if there are administered by rapid IV injection
Differentials to consider in MG
Other causes of ptosis
Muscular dystrophies
Familial hypokalaemic paralysis
What is the Eaton-Lambert myasthenic syndrome?
Paraneoplastic syndrome
Antibodies (usually against small cell carcinoma of the bronchus) block calcium channels in presynaptic terminals which inhibits ACh release
How does Eaton-Lambert differ from MG?
In Eaton-Lambert the eyes are not usually as affected, proximal muscle weakness is common and strength is initially increased by repetitive movement
Treatment for Eaton-Lambert
Diamondpyridine - blocks presynaptic potassium efflux thus potentiating Ca channel opening and ACh release
