neuromuscular disorders Flashcards
signs/symptoms of muscle disease
- Myalgia
- Muscle weakness – often specific patterns of weakness depending on cause – proximal etc
- Wasting
- Hyporeflexia
- Myotonia
o Failure of muscle relaxation after use
o Chloride channel - Fasciculations
o Can be normal – stress, caffeine, fatigue
o Occur in denervated muscle which becomes hyperexcitable
o Usually a sign of disease in motor neuron – not muscle
presynaptic + postsynaptic neuromuscular disorders
presynaptic
- botulism - clostridium botulinum
- lambert eaton syndrome
postsynaptic
- myasthenia gravis
clostridium botulinum
gram positive anaerobic bacillus
produces botulinum toxin
- a neurotoxin which irreversibly blocks the release of acetylcholine
–> often affects bulbar muscles + ANS
pathophysio of clostridium botulin
botulin toxins cleaves preynaptic protein involved in vesile formation + blocks vesicle docking with presynaptic membrane
causes of clostridium botulinum
organism found in soil
from eating contaminated food (tinned)
IV drug use - black tar heroin
features + treatment of clostridium botulinum
patient fully conscious with no sensory disturbance
flaccid paralysis
diplopia
ataxia
bulbar palsy
Mx = botulism antitoxin + supportive care - only effective if given early
lamber eaton myasthenic syndrome
progressive muscle weakness, improves with increased use as a result of damage to neuromuscular junction
assoc with small cell carcinoma - antibodies produced by immune system against voltage gate calcium channles in small cell lung cancer
pathophysio of lambert eaton
antibodies target + damage the voltage gated calcium channels in PREsynaptic terminals of the neuromuscular junction where motor nerves communicate with muscle cells
These voltage-gated calcium channels are responsible for assisting in the release of acetylcholine into the synapse of the neuromuscular junction
This acetylcholine then binds to acetylcholine receptors + stimulates a muscle contraction
When these channels are destroyed, less acetylcholine is released into the synapse
(antibodies to presynaptic calcium channels leads to less acetycholine vesicle release)
presentation of lambert eaton syndrome
symptoms develop slowly
proximal muscles - proximal leg weakness
diplopia - intraoculare muscles
ptosis - levator muscles
dysphagia - oropharyngeal muscles
autonomic dysfunction - dry mouth, blurred vision, impotence
reduced tendon reflexes - reflexes become temporarily normal after a period of strong muscl contraction = post-tetanic potentiation
worsens with increased temperature
treatment of lambert eaton syndrome
3,4 diaminopyridine (amifampridine)
- allows more acetylcholine to be released at junction
- blocks voltage gated potassium channels in presynaptic cells
check for underlying small cell lung cancer
myasthenia gravis
autoimmune condition that causes muscle weakness that gets progressively wore with activity + improves with rest
bimodal peaks - women (30s), men (60-70s)
assoc with thymic hyperplasia/thymoma
myasthenia gravis pathophysio
Acetylcholine receptor antibodies are produced by the immune system
o These bind to post synaptic neuromuscular junction receptors blocking stiumulation to trigger muscle contractions
As the recptors are used more during activity, more of them become blocked up
o This leads to less effective stimulation of the muscle with increased activity
o This improves with rest as more receptors are freed up again
These antibodies also activte the complement system triggering inflammatory cascade within the neuromuscular junction
o Leading to damge to cells at postsynaptic membrane – worsens symptoms
myasthenia gravis presentation
weakness that gets worse with muscle use + improves with rest
- worse at end of day
proximal muscles
- diplopia, ptosis, dysphagia
- weak facial movements - chewing
- slurred speech
- progressive weakness with repetitive movements
thymectomy scar
myasthenia gravis examination
repeated blinking -> exacerbates ptosis
prolonged upwards gaze - exacerbates diplopia on further movements
abduct one arm 20 times - then compare both sides
test forced vital capacity(FVC) - reduced
myasthenia gravis investigation
testing for antibodies
- acetylcholine receptor (Ach-R) antibodies
- muscle-specific kinae (MuSK)
- LRP4
single fibre EMG
CT or MRI of thymus - thymoma
management of myasthenia gravis
pyridostigimine (acetylcholinesterase inhibitor)
- increases amount of acetylcholine in the neuromuscular junction + improves symptoms
immunosuppression - prednisolone, azathioprine
- suppress the production of antibodies
thymectomy
which antibiotic should be avoid in myasthenia gravis?
gentamicin
emergency treatment for myasthenia gravis
plasma exchange or immunoglobulin
polymyositis + dermatomyositis
autoimmune condition where inflammation is in the muscle
polymyositis = condition of chronic inflammation of muscles
dermatomyositis = connective tissue disorder where there’s chronic inflammation of skin + muscle
can be caused by underlying malignancy (making them paraneoplastic syndromes
Polymyositis + dermatomyositis presentation
muscle pain, fatigue, WEAKNESS - worsens over months
occurs bilaterally + typically affects proximal muscles
mostly affects shoulder + pelvic girdle
develops over weeks
other organ involvement
- interstitial lung disease + resp muscle weakness
- dysphagia
- myocarditis
- fever, weight loss, raynauds
dermatomyositis skin features
- Gottron lesions – scaly erythematous patches on knuckles, elbows + knees
- Photosensitive erythematous rash – on back, shoulders, neck
- Purple rash on face + eyelids (helitope rash)
- Periorbital oedema – swelling around eyes
- Subcutaneous calcinosis – calcium deposits in subcutaneous tissue
Polymyositis + dermatomyositis investigations
definitive diagnosis = muscle biopsy
creatine kinase = GOLD
- usually over 1000 (normal - 300ish)
autoantibodies
- anti-jo
- anti-Mi-2
- anti-nuclear
electromyography (EMG) - increased fibrillation, abnormal motor potentials, repetitive discharges
Polymyositis + dermatomyositis management
rheum, physio, occupational
new cases assess for cancer
steroids = 1st line
if inadequate
- immunosuppressants - azathioprine
- IV immunoglobulins
biological therapy - infliximab
muscular dystrophy + a key sign of it
group of genetic conditions that cause gradual weakening + wasting of muscles
gower’s sign
- Proximal muscle weakness of pelvic girdle
- Use hands on legs to helps them stand up
myotonic dystrophy mode of inheritance
commonest muscular dystrophy
autosomal dominant
presents in adulthood - 20s
trinucleotide disorder with anticipation
myotinic dystrophy presentation
prolonged muscle weakness
prolonged muscle contractions (myotonia) - patient unable to let go after shaking someones hand, let go of door knob
dysarthria, wasted SCM
cataracts
cardiac arrhythmias, testicular atrophy
bilateral ptosis, frontal balding
duchennes muscular dystrophy
x linked recessive
- affected mother has 50% chance of giving to kids
- dystrophin deficiency/absence - dystrophin is protein that helps hold muscles together
life expectancy 25-35yrs
usually dead by 20 due to cardio/resp problems
difference in pathophysio between beckers and duchennes muscular dystrophy
in beckers dystrophy, dystrophin is present but levels are low - progresses much more slowly
beckers also presents older (8-12) and live longer ish
duchennes presentation
- Boys aged 1-6 – onset 3-4yrs
- Developmental delay
- Proximal muscle waster
- Toe walking
- Exaggerated lumbar lordosis
- Pseudohypertrophy of calves
- Gowers manoeuvre
- Dystrophin also present in brain – some boys present with learning difficulties/cognitive problems
complication of duchennes
dilated cardiomyopathy
management of duchennes
no cure
steriods may delay progression
creatine supplementation
MDT, resp support
spinomuscular atrophy type 1
- Autosomal recessive
- Abnormal messenger RNA – doesn’t get transcribed
- Can get corrected by RNA therapy maybe
- Progress loss of anterior horn cells in spinal cord + brain
- Autosomal recessive
o SMN1 deficiency, on chromosome 5 - Proximal muscle weakness
- Hypotonia
- Tongue fasciculation
prader-willi
- Chromosome 15
- floppy baby
- Neonate = weak muscles, poor feeding, slow development
- Child = constantly hungry, obesity, T2DM
- Hypogonadism, learning difficulties
mx - Orlistat
rhabdomyolysis pathophysio
Muscle cells (myocytes) undergo cell death apoptosis)
Cell death results in muscle cells releasing –
o Myoglobin – causing myoglobinuria
o Potassium
Hyperkalaemia -> arrhythmias -> cardiac arrest
o Phosphate
o Creatine kinase
Breakdown products are filtered by the kidney + cause injury to kidney
o Myoglobin is toxic to kidney in high conc
o Results in AKI -> causes further accumulation of breakdown products in blood
rhabdo investigations
Creatine kinase (CK)
o Will be in thousands-hundreds of thousands
o Higher CK increases risk of kidney injury
Myoglobinuria = myoglobin in urine
o Gives red-brown colour
o Causes urine dipstick to be positive for blood
U&Es – AKI, hyperkalaemia
ECG – hearts response to hyperkalaemia (tall tented Twaves)
rhabdo causes
seizure
collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
ecstasy
crush injury
McArdle’s syndrome
drugs: statins (especially if co-prescribed with clarithromycin)
rhabdo mx
IV fluids
(IV sodium bicarb, IV mannitol (increase GFR))
