MUSCLE AND NMJ DISORDERS Flashcards
What is a myopathy?
A disease of muscle in which the muscle fibres do not function properly, resulting in muscular weakness
Inherited myopathies?
Muscular dystrophies
Inherited biochemical defects causing myopathy e.g. glycogen storage diseases, mitochondrial myopathy
Acquired myopathies?
Polymyositis and dermatomyositis
Drugs e.g. statins, fibrates, steroids, antipsychotics, colchicine
Infections e.g. HIV, influenza, EBV
Alcoholism abuse
Endocrine disorders - thyroid, parathyroid, pituitary or adrenal dysfunction
Systemic inflammatory conditions - SLE, RA, scleroderma, Sjögren, sarcoidosis
Electrocute imbalance
What is the clinical spectrum of statin-induced myopathy?
Myalgia
Myositis
Rhabdomyolysis
Clinical features of statin-induced myopathy?
Fatigue
Muscle pain
Muscle tenderness
Muscle weakness
Nocturnal cramping
Tendon pain
Symptoms proximal, generalised and worse with exercise
What is myalgia?
Muscle pain
What is myositis?
A group of rare inflammatory conditions that cause muscle weakness
Most common types of myositis?
Dermatomyositis
Polymyositis
What is dermatomyositis?
An autoimmune, inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions
May be idiopathic, associated with connective tissue disorders or underlying malignancy
Its polymyositis with skin involvement
Which malignancies is dermatomyositis most commonly associated with?
Ovarian
Breast
Lung
Which patients with dermatomyositis are most likely to have an underlying malignancy?
If the patient is older
(Screen for underlying malignancy folllowing a diagnosis of dermatomyositis)
Skin features of dermatomyositis?
photosensitive erythematous rash
macular rash over back and shoulder
heliotrope rash in the periorbital region
Gottron’s papules - roughened red papules over extensor surfaces of fingers
‘mechanic’s hands’: extremely dry and scaly hands with linear ‘cracks’ on the palmar and lateral aspects of the fingers
nail fold capillary dilatation
Presentation of dermatomyositis and polymyositis?
Gradual onset over weeks-months, symmetrical, proximal muscle weakness (tends to be neck, shoulder and pelvis first)
Causes diffiuclties standing from a chair, climbing stairs or lifting overhead
May be myalgia in 33%
Others:
Raynauds
Respiratory muscle weakness, interstitial lung disease
Dysphagia and dysphonia
Investigations for dermatomyositis?
Elevated creating kinase
High ESR
Autoantibodies:
ANA - 80% positive
Antibodies to aminoacyl-tRNA synthetases in 30%
Malignancy screen for adults - CT chest/abdomen/pelvis
Electromyograhy and muscle biopsy may be required
Management of polymyositis and dermatomyositis?
Physiotherapy and OT to help with muscle strength and function
Corticosteroids
What is Polymyositis?
An autoimmune inflammatory condition of muscles
May be idiopathic, associated with connective tissue disorders or malignancy
Dermatomyositis is a variant of the disease where skin manifestations are prominent
Pathophysiology of polymyositis?
T-cell mediated cytotoxic process directed against muscle fibres
Age and gender for polymyositis?
Middle aged
Female:male 3:1
Investigtaions for polymyositis?
Elevated CK
Muscle enzymes e.g. LDH, AST and ALT will also be elevated
EMG and muscle biopsy
Anti-synthetase antibodies
What are muscular dystrophies?
Genetic conditions that cause gradual weakening and wasting of the muscles
Types of muscular dystrophies?
Duchennes muscular dystrophy
Beckers muscular dystrophy
Myotonic dystrophy
Facioscapulohumeral muscular dystrophy
Oculopharyngeal muscular dystrophy
Limb-girdle muscular dystrophy
Emery-Dreifuss muscular dystrophy
What is Gower’s sign?
How children with proximal muscle weakness use a specific technique to stand up from a lying position
They get onto their hands and knees, push their hips back and up and then shift their weight backwards and transfer their hands to their knees
Whilst keeping their legs mostly straight they walk with their hands up their legs to get their upper body erect
This is because the muscles around the pelvis are not strong enough to get their upper body erect without the help of their arms
Management of muscular dystrophy?
No curative treatment
Management is aimed at allowing the person to have the highest quality of life for the longest time possible - usually involves OT, PT, medical appliances, surgical and medical management of complications e.g. spinal scoliosis and HF
Cause of Duchenne muscular dystrophy?
Defective been for dystrophin (the protein that helps hold muscles together) on the X-chromosome
What pattern of inheritance if Duchennes muscular dystrophy and why?
X-linked recessive
This is because it’s caused by defective dystrophin on the X-chromosome
Male vs female presentation of duchennes muscular dystrophy?
Female carriers of the condition do not usually notice any symptoms - this is because they have 2 X chromosomes. This means if they have children they have a 50% chance of being a carrier if female or having the condition if male
Males will be symptmatic
Symptoms and signs of duchennes muscualr dystrophy?
Progressive proximal muscle weakness from 5 years - typically starts around pelvis
Usually wheelchair bound by 12
Calf pseudohypertrophy
Gowers sign
Intellectual impairment in 30%
Investigations for duchenne muscular dystrophy?
Raised CK
Genetic testing for definitive diagnosis
Which heart condition is duchenne muscular dystrophy associated with?
Dilated cardiomyopathy
Prognosis of duchenne muscular dystrophy?
most children cannot walk by the age of 12 years
patients typically survive to around the age of 25-30 years
Main cause of death is cardio-respiratory failure
How can we slow the progression of duchenne muscular dysophy?
Steroids may improve muscle strength and function for 6 months-2 years
Ataluren is a newer med that can be given to children 2 or older who can walk
Creative supplementation can improve muscle strength
What type of mutation occurs in duchenne muscular dystophy?
Frameshift mutation in the dystrophin gene resulting in 1 or both of the binding sites being lost
What type of mutation occurs in Becker muscular dystophy?
Non-frameshift insertion in the dystrophin gene resulting in both bindings sites being preserved = a milder form than duchenne as dystrophin minatians some of its function
Important features of Beckers muscular dystrophy?
Clinical symptms and signs develop after 10 years of age
Intellectual impairment is much less common than beckers muscular dystrophy
Some patients require wheelchairs in late 20s or 30s, whilst others can with with assistance into later adulthood
Often live into their 40s or beyond
What is myotonic dystophy?
Presentation?
A genetic condition causing progressive msucle weakness and wasting, prolonged muscle contractions, cataracts and cardiac arrhythmias
Presents in adulthood
What is facioscapulohumeral muscular dystrophy?
Presentation?
A muscular dystrophy that presents in childhood
Causes weakness around the face that progresses to the shoulders and arms
A classic initial symptom is sleeping with their eyes slightly open and weakness in pursing their lips e.g. unable to blow their cheeks out without air leaking from mouth
What is oculopharyngeal muscular dystrophy?
Presentation?
A muscualr dystrophy that usually presents in late adulthood with weakness of ocular muscles and pharynx
Typically presents with bilateral ptosis, restricted eye movement and swallowing problems
It can affect the muscles around the limb girdles to a varying degree
How does limb-girdle muscular dystrophy present?
In teenage years with progressive weakness around the hips and shoulder (limb girdles)
How does emery-Dreifuss muscular dystrophy present?
Presents in childhood with contractures, most commonly in the elbows and ankles
This shortening of muscles and tendons restricts the range of movement in limbs
Patients also suffer with progressive weakness and wasting of muscles, starting with upper arms and lower legs
Structure of muscles
Each muscle is surrounded by the epimysium
Within each muscle, fascicles (bundles of muscle fibres) are bound together by the perimysium
Each muscle fibre is surrounded by endomysium
What is the synaptic end bulb?
The nervous system component of the neuromuscular junction - its where the tip of the axon terminal enlarges and terminates close to the muscle fibre
What is the motor end plate?
The muscular component of the neuromuscular junction
Neurotransmitter for neuromuscular junctions?
Acetylcholine
Outline how transmission of ACh across the synaptic cleft occurs?
ACh is stored in vesicles in synaptic end bulb
As the electrical signal approaches the synaptic end bulb it stimulates the inflow of Ca2+by opening voltage-gated channels in the cell membrane of the neurone
The increase of Ca2+ causes synaptic vesicles to move towards and fuse with the neuron’s cell membrane. Once fused, synaptic vesicle exocytose the ACh into the synaptic cleft
ACh then moves across the cleft towards the motor end plate of the muscle fiber
The binding of 2 molecules of ACh to an acetylcholine receptor open the ion channel in the receptor and allows influx of Na+ into the muscle fibre
This initiates an action potential that travels towards the ends of the muscle fibre to cause contraction
What is lambert-Eaton myasthenic syndrome?
An autoimmune condition affecting the neuromuscular junction
Cause of lambert-Eaton syndrome?
Most commonly it occurs with small cell lung cancer, and to a lesser extent, breast and ovarian cancer as a paraneoplastic syndrome
It may occur independantly as an autoimmune disorder
Pathophysiology of Lambert-Eaton syndrome?
Antibodies against voltage-gated Ca2+ which target and damage the calcium channels in presynaptic membranes of the neuromuscular junctions
This means less ACh can be released into the synapse = weaker signal and reduced muscle contraction
Presentation of Lambert-Eaton syndrome?
Proximal muscle weakness but repeated muscle contraction leads to increased muscle strength
Limb-girdle weakness
Reduced or absent reflexes
Autonomic symptoms: blurred vision, dry mouth, impotence, difficulty micturition
Diagnosis of Lambert-Eaton syndrome?
Nerve conduction studies to show after exercise, muscle action potentials increase
Chest CT to look for lung cancer
Management of Lambert-Eaton syndrome?
Treating underlying malignancy if present
Immunosuppression e.g. prednisolone or azathioprine
3,4-diaminopyridine is being trialled
IV immunoglobulin therapy and plasma exchange may also be beneficial
What is myasthenia gravis?
An autoimmune disorder resulting in insufficient functioning acetylcholine receptors
Causes muscle weakness that progressively worsens with activity and improves with rest
Men vs women prevalence of myasthenia gravis?
Typically affects women under 40 more and men over 60 more
Overall women:men 2:1
Antibodies in myasthenia gravis?
Antibodies to acetylcholine receptors in up to 90%
Associated disorders to myasthenia gravis?
Thymomas - 15%
Autoimmune disorders e.g. pernicious anaemia, autoimmune thyroid, SLE, RA
Thymic hyperplasia in up to 70%
Pathophysiology of myasthenia gravis?
Acetylcholine receptor antibodies bind to postsynaptic acetylcholine receptors, blocking them and preventing stimulation by acetylcholine
The more receptors used during muscle activity, the more they become blocked
With rest, receptors are cleared and symptoms improve
The antibodies also activate the complement system which can lead to cell damage at the post synaptic membrane, further worsening symptms
Presentation of myasthenia gravis?
Muscle fatigability
Diplopia - Extraocular muscle weakness
Proximal muscle weakness - face, neck, limb girdle e.g. diffiuclty climbing stairs or raising hands above head
Ptosis - eyelid weakness
Dysphagia
Fatigue in jaw when chewing
How can you elicit fatiguability in the muscles?
Repeated blinking will exacerbate ptosis
Prolonged upward gazing will exacerbate diplopia on further testing
Repeated abduction of 1 arm 20 times will result in unilateral weakness when comparing sides
Investigations for myasthenia gravis?
Single fibre electromyography - high sensitvity
CT thorax to exclude thymoma
CK - will be normal
Antibodies to ACh receptors
Tensilon test
What is tensilon test and why is it not commonly used anymore?
Giving IV edrophonium (a reversible acetylcholinesterase inhibitor). This temporarily reduces the muscle weakness
This has a risk of cardiac arrhythmias
Management of myasthenia gravis?
Long-acting acetylcholinesterase inhibitors e.g. pyridostigmine
Immunosuppression will eventually need to be used in addition. Usually prednisolone - this suppresses production of antibodies
Thymectomy - can improve symptoms even in pt without a thymoma
What is a myasthenic crisis?
A potentially life-threatening complication of myasthenia gravis that causes an acute worsening of symptoms such as respiratory muscle weakness which can lead to respiratory failure
Often triggered by another illness e.g. RTI
Pt may require NIV or mechanical ventilation
Management of a myasthenic crisis?
Plasmapheresis - removal of plasma which contains the antibodies
IV immunoglobulins
Exacerbating factors for myasthenia gravis?
Exertion
During the day
Drugs:
Penicillamine
Quinidine, procainamide
Beta blockers
Lithium
Phenytoin
Antibiotics: gentamicin, macrolides, quinolones, tetracyclines
What is congenital myasthenic syndrome?
An inherited neuromuscular disorder caused by defects of several types at the NMJ
There are many causes e.g. acetylcholine receptor deficiency or choline acetyltransferase deficiency
What causes botulism?
Clostridium botulinum - a gram positive anaerobic bacillus that produces botulinum toxin which blocks release of acetylcholine
Where can you get clostridium botulinum from?
Eating contaminated food e.g. tinned food
IV drug use
Features of botulism?
Fully conscious with no sensory disturbance
Flaccid paralysis
Diplopia
Ataxia
Bulbar palsy
What is bulbar palsy?
A set of symptoms and signs linked to the impaired function of cranial nerves 9, 10, 11 and 12
Causes tremulous lips, weak and wasted tongue, drooling due to dysphagia, absent palatal movements, dysphonia due to vocal cord paralysis, articulation diffiuclties due to dysarthria
What is a myeloradiculopathy?
Disorders that affect the spinal cord and the nerve roots exiting the spinal cord
E.g. compression of spinal cord by herniated disc
What is a ganglionopathy?
Disorder of the ganglion (collection of nerve cell bodies outside the CNS)
Anatomical sites that can cause weakness if disease?
Anterior horn cell
Peripheral nerve
Neuromuscular junction
Muscle
Anterior horn cell lesions in general give rise to what symptoms?
Weakness
Muscle wasting
Fasciculations
Can be focal but more typically widespread
Where does weakness typically affect in myopathy vs peripheral neuropathy?
Peripheral neuropathy - distal
Myopathy - proximal
Neuromuscular junction lesions in general give rise to what symptoms?
Fatiguable weakness improved by rest
Congenital anterior horn cell disorders
Familial motor neuron disease
Familial spinal-muscular atrophy
What is poliomyelitis?
An infectious disease caused by a poliovirus of the anterior horn cells
Can affect motor cranial nerves
A small proportion may go on to develop post-poliomyelitis syndrome years after. Causes muscle fatigue, decreased endurance
Why type of nerve disorder does a brachial plexus injury cause (broad term!)?
A polyradiculopathy
What is erb’s palsy?
A superior trunk injury (C5 and C6)
Occurs in newborns e.g. after traction injuries
Causes the water tip position - shoulder adducted and internally rotated with the elbow extended and pronated, wrist flexed
What is klumpke’s palsy?
Lower trunk injury (C8-T1)
Occurs in newborns usually following traction injury
Causes paralysis of intrinsic hand muscles, flexors of risk and fingers = claw hand
Causes C8-T1 dermatology distribution numbness
Involvement of T1 may result in horners syndrome
Axonal vs demyelinating neuropathies on nerve conduction studies
Axonal - reduction in amplitude
Demeylinating - reduction in conduction velocity by >50%
Types of demyelinating polyneuropathy?
Inflammatory demyelinating polyneuropathy
Immune-mediated demyelinating polyneuropathy
Paraproteinaemia e.g. myeloma
Acute polynueropathies?
Acute inflammatory and immune mediated demyelinating polyneirothy and other types e.g. Guillain barre syndrome
Diphtheria
Porphyria
Toxins e.g. thallium
Tick bite
Paraneoplastic syndromes - rare
Chronic polyneuropathy causes?
Deficiencies e.g. B12
Alcohol
Heavy metals and solvents
Drug toxicity
Uraemia
Diabetes
Vasculitis
Cryoglobulinaemia
Sarcoidosis
Peripheral vascular disease
Lyme disease
Carcinomatous meningitis
Critical illness neuropathy e.g. in ICU for a long time
What is the hanging jaw sign?
Inability to hold the jaw open due to weakness in facial muscles
Seen in myasthenia gravis
Presentation of steroid induced myopathy?
Symmetrical pelvic girdle muscle weakness
Quadriceps wasting
May have gait changes e.g. Trendelnburg gait
