Myopathies, NMJ DX and MND Flashcards
Name some disorders of motor function
Anterior Horn - motor neuron diseases
Peripheral nerve - neuropathies
Neuromuscular junction - pre and post synaptic
Muscle
What does a motor unit consist of?
Anterior horn Cell
Peripheral nerve
NMJ
Muscl
What are the two types of nerve conduction
Decremental
Saltatory
What happens at the neuromuscular Junction?
Nerve cell is depolarised -> leading to Ca++ channel opening –> Increased Ca++ concentration –> release ACh into synaptic cleft
1- Ach + AchE + acetate –> Ch -> inside cell
2. Binds to AchR -> EPSP -> MFAP -> muscle contraction (CA2+ enters T tubules, causes Ca + release from the sarcoplasmic reticulum) -> Ca+ binds to troponin (troponin removes tropomysin, actin exposed)
–> contraction - > myosin cross bridges alternatively attach to actin & detach
Ca2+ removed to SR
what is a myopathy?
• Primary disease of muscle • Weakness - Symmetric - Proximal > distal (large muscles more susceptible to damage) - Atrophy
- Myotonia (spontaneous contraction), myalgia (muscle pain) & cramps
- Sensatoon preserved
- Reflexes preserved (unless severe)
What would you see in neurogenic disease?
- Similar characteristics to myopathies
- Deep tendon reflexes lost
- Fasciculations
- Segmental pattern in MND
- Combined UMN & LMN features in MND
- Sensory symptoms in peripheral neuropathy
What would you see in a NMJ post synaptic condition?
- Variable weakness – may increase through the day or increased activity
- Often have involvement of extraocular muscles – diplopia & ptosis (MG)
- > 95% have facial weakness (MG)
- Other muscle groups – bulbar, respiratory, limbs & trunk
- Fatigue
- Muscle wasting is uncommon
- Tendon reflexes are usually preserved
- Sensory examination is normal
What would you see in a NMJ pre synaptic condition?
• Rare
• Lambert Eaton Myasthenic syndrome
• LEMS weakness, proximal > distal, legs > arms
• LEMS weakness improves with brief sustained exercise & absent tendon reflexes may appear with exercise
• LEMS never begins with ocular muscle weakness
• May have an associated sensory neuropathy (LEMS)
• Autonomic symptoms (LEMS) – dry eyes/mouth, impotence, blurred vision, bladder, hypohidrosis
• Botulism – diffuse weakness, bulbar weakness and ptosis/EOM weakness, autonomic symptoms
o Botulism can develop very rapidly
what testing would you use for myopathies?
and what is the goal?
Electrodiagnostic Testing
Goals: to localise (muscle, NMJ (fibre type), nerve, anterior horn) the site of dysfunction within the motor unit & to determine the severity
EMG testing:
Electromyography is a test that checks the health of the muscles & the nerves that control the muscles.
A very thin needle electrode is inserted through the skin into the muscle.
This electrode on the needle picks up the electrical activity given off by your muscles. T
EMG is most often used when people have symptoms of weakness, and examination shows impaired muscle strength. It can help to tell the difference between muscle weakness caused by injury of a nerve attached to a muscle & weakness due to neurologic disorders. • Stick needle into muscle & record APs. Normal muscle should be electrically silent • Look for abnormal spontaneous activity o Fibrillation potential o Positive sharp waves o Fasciculations o Complex repetitive discharges o Myokymia o Myotonia
What would you see in EMG testing if it was a myopathy?
o In a myopathic process the muscle fibers are dropping out – that motor unit AP (sum of individual motor fiber APs) will be smaller
• The waveform is smaller
- Rapid recruitment
- Short duration
- Low amplitude
- Polyphasic
- Caution – long duration MUPs can be seen in chronic myopathies, IBM, infiltrative processes involving muscle & nerve
What would you see in EMG testing if it was a neurogenic process
o In a neurogenic process (Motor unit)
The anterior horn cells die back, so the muscles they were supplying become deinnervated. Reinnervation occurs in the periphery by neighbouring axon fibers, so when you do EMG the AP is much bigger (as there are more individual fibers connecting to that motor unit)
- Reduced recruitment
- Increased duration
- Increased amplitude
- Polyphasia
Myopathies can be aquired or congenital./hereditary
- What are some aquired aetiologies
- Inflammatory
- Infection
- Cancer related
- Endocrine
- Medicine
Myopathies can be aquired or congenital./hereditary
- What are some congenitl aetiologies
- Muscular dystrophies
- Mitochondrial
- Metabolic
- Congenital myopathies
What are some common findings in inflammatory myopathies?
Symmetrical proximal muscle weakness (except IBM)
Increased serum levels of muscle-derived enzymes
Non-suppurative inflammation of skeletal muscle (not infective)
What are some common causes of inflammatory myopathies?
- inclusion body miositis
- polymyositis
- dermatomyositis
What are muscular dystrophies
inherited disorders, often presenting in childhood that are characterised by progressive degeneration of muscle fibers leading to muscle weakness & wasting
Describe Duuchenne’s muscular dystrophy
- X-linked; the most severe form, affects males
- Starting by 3-7 years old, progressive muscle weakness leading to wheelchair by 12 y.o.
- Most die by 20 of respiratory failure
• Signs
- Involves mainly the shoulder & pelvic girdles
- Muscle hypertrophy – enlarged muscles, especially the calf
- Increases with age
- Most commonly due to muscle fibrosis (increased muscle bulk caused initially by an increase in the size of the muscle fibers & then as the muscle atrophies, by an increase in fat & CT)
what is a Motor neuron disease
• Clinical & neuropathologic deficits of UMN & LMN
LMN disease symptoms
Flaccid Decreased tone Decreased muscle stretch reflexes Profound muscle atrophy Fasciculations present May have sensory disturbance
UMN disease symptoms
Spasticity Increased tone Increased muscle stretch reflexes Minimal muscle atrophy Fasciculations absent May have associated sensory disturbances
Type of MND: ALS
UMN & LMN
Muscle weakness & atrophy, in combination with spasticity. A subset of patients have additional frontal executive dysfunction (frontotemporal dementia – rarely)
Relentlessly progressive disease & almost uniformly fatal within 3-5 years, usually because of respiratory failure as a result of diaphragmatic weakness
Type of MND: PLS
UMN
Weakening of the muscles & spasticity
Type of MND: SMA
Type I (Werdnig-Hoffman’s disease) present in early infancy, sometimes even immediately after, or before birth with – severe hypotonia & weakness.
Type II: similar clinical deficits but noticed later
Type III: slowly progressive weakening
Type IV: adult onset weakening
What are the diagnostic criteria for ALS?
Diagnostic Criteria (by clinical exam, EMG & pathology)
• Definite ALS: progressive disease with
-UMN & LMN signs in bulbar (ie cranial nerves) & 2 spinal regions (ie cervical, lumbar)
- UMN & LMN sings in 3 spinal regions
• Probable ALS: Progressive disease with –
- UMN & LMN signs in 2 regions and
- UMN signs in a region rostral to the LMN signs
Name the presynaptic NMJ disorders
Lambert Eaton Myasthenic Syndrome
Botulism
presynaptic NMJ disorders: LEMS
o Anti-voltage gated calcium channel (Anti-VGCC) antibodies (15% will have negative antibodies)
o Associated with small cell lung cancer (60%)
o Reduced K+ stimulated Ca++ flux into pre-synaptic terminals = reduced Ca++ dependent quantal ACh release
o Manage primary neoplasm
o 3,4-diaminopyridine
o Nerve conduction study
o Immunosuppression
presynaptic NMJ disorders: Botulism
o Clostridium botulinum – obligate anaerobe
o Seven neurotoxic types of botulinum toxin – A to G
o Produces botulinum toxin which binds to motor neurons, is endocytosed & remains at the NMJ, blocking the release of neurotransmitter ACh, hence preventing the excitation of muscles (affects NMJ, autonomic nerves)
o Interferes with SNARE presynaptic protein
o Characterised by the development of flaccid paralysis
Name the most common POST SYNAPTIC NMJ disorder
Myasthenia Gravis - Autoimmune disorder whereby circulating antibodies block the ACh receptor on postsynaptic NMJ (inhibiting the excitatory effect of ACh)
What are the subtypes of MG?
How do you test?
Subtypes MG: ocular, generalized, bulbar or distal involvement
Testing – pharmacological, serological, electrodiagnostic
Pharmacological testing – endrophonium (tensilon)
Antibody testing
- AChR antibodies positive in 85-90%generalised MG
- AChR antibodies positive 50-70% ocular MG
- MuSK antibodies in 30-70% AChR antibody negative patients
REPETITIVE NERVE STIMULATION
• Abnormal junction → influx of calcium, as this increases, the efficiency of NT release starts plateauing. First response is normal, but subsequent responses are smaller in size
Treatment of MG
• Symptomatic – acetylcholinesterase inhibitors, or immunosuppressants
