Muscle and nerve diseases Flashcards
Where does the UMN synapse first?
The anterior horn
What are the 4 components of muscle contraction?
Structural components
Contractile mechanism – myosin fibrils embedded in membrane and it shortens as it contracts
Excitation-contraction coupling (ion channels)
Energy system – can’t contract muscle without energy
Symptoms of muscle disease? (7)
Weakness of skeletal muscle
Short of breath (respiratory muscles)
Poor swallow / risk of aspiration (bulbar muscles)
Cardiomyopathy
Cramp (repetitive!)
Pain and stiffness
Myoglobinuria
What is myoglobinuria?
Muscle breaks down and is excreted in urine – makes urine black, looks like blood
Symptoms of muscle disease in babies?
Poor suck / feeding / failure to thrive / floppy
Signs of muscle disease?
Wasting / hypertrophy
Normal or reduced tone and reflexes (usually loss
of muscle tone)
Motor weakness…NOT sensory
Why might hypertrophy result from a muscle disease?
Muscle cannot relax
Investigations for muscle disease (5)
History and examination
Creatine Kinase (CK)
EMG - electromyography
Muscle biopsy - look at structure, biochem and inflammation
Genetic testing
What is significant about creatine levels?
sign of muscle fibre degeneration - chewing up muscle
Genetics and muscle disease
Most congenital diseases are genetic however this doesn’t mean they are present at birth – can come up later on in life
Genetics can affect all 4 components of muscle contraction
How do congenital / genetic muscle diseases affect each component
Structural: muscular dystrophies
Contractile: congenital myopathies - hypotonia and weakness, usually present from birth, with a static or slowly progressive
Coupling: channelopathies - diseases caused by disturbed function of ion channel subunits or the proteins that regulate them
Energy: enzymes / mitochondria
How do acquired muscle diseases affect muscles
Metabolic (increased or low Ca2+, K+) – severe illness
Endocrine (thyroid, adrenal, vit D- rickets?)
Inflammatory muscle disease
Iatrogenic: medication (steroids / statins) - ie steroids used to treat myopathy then result in further myopathy
What is Myopathy?
Myopathy is a disease of the muscle in which the muscle fibers do not function properly.
This results in muscular weakness.
Describe what Muscular dystrophies are
Gradually cause the muscles to weaken, leading to an increasing level of disability.
Young or older onset
progressive, variable severity
Cell degeneration (often high CK)
No specific treatments yet
Give examples of some muscular dystrophies
Duchenne’s/Becker’s
Duchenne’s - aggressive and will limit life where as becker’s has milder symptoms and has a later onset. They are 2 alterations of same gene/protein
Facioscapulohumeral
limb girdle
Myotonic dystrophy - ong-term genetic disorder that affects muscle function - muscles contract and can’t relax - cataracts is common symptom - multi-system disease
What are channelopathies
disorders of Ca2+, Na+, K+ and Cl- channels
often paroxysmal symptoms e.g. periodic paralysis / myotonia
partially treatable
Metabolic myopathy
Exercise induced:
early = disorders of carbohydrate metabolism
late = disorders of lipid metabolism
Mitochondrial problems
Partially treatable
Inflammatory muscle disease
Polymyositis
It can be associated with a skin rash and is then called ‘dermatomyositis’
Can occur at any age, acute or subacute
painful, weak muscles
symptoms can be a sign of existing cancer or may also increase the risk of malignancy - tumour screen done
High CK levels
Tests for inflammatory muscle diseases
EMG
Biopsy - polymyositis - CD8 T cells
Dermato - humeral-mediated, B cells and CD4 cells
Treatment for inflammatory muscle diseases
immunosuppression
What are the classifications of muscle disease?
Muscular dystrophies - usually genetic - to do with structure of the muscle
Channelopathies - usually episodic
Metabolic muscle disease - an issue with the way the muscle uses energy, usually due to enzymes
Inflammatory muscle disease
Congenital myopathies
Iatrogenic - medication - statins cause inflammation or degeneration of the muscles
What is Myasthenia Gravis
Disorder of the neuromuscular junction - long-term neuromuscular disease
Investigations for Myasthenia Gravis
Antibodies
If negative do Neurophysiology (Repetitive stimulation, Jitter)
CT chest (thymoma about 10% have underlying)
Treatment for Myasthenia Gravis (4)
Symptomatic
- Acetylcholinesterase inhibitor (pyridostigmine)
Immunosuppression
- Prednisolone
- Steroid saving agent (e.g. azathioprine)
Immunoglobulin / plasma exchange
Thymectomy - antibody production can be as a result of an over active thymus - even in the case where there is no thymoma
What is peripheral nerve disease (neuropathy)?
disease of the nerves beyond the brain and spinal cord
What does a peripheral nerve consist of? (4)
Sensory axons
- Small fibres (pain + temperature)
- Large fibres (joint position sense + vibration)
Motor axons
Autonomic axons
Nerve sheath (myelin)
Generalised peripheral neuropathy affect
Motor / sensory / both
+/- autonomic features
A lesion of individual peripheral nerve will cause what?
Compressive / entrapment neuropathy - direct pressure on a nerve - causes pain, tingling, numbness
Vasculitic (mononeuritis multiplex) - If nerve doesn’t receive blood from the vasovasorum there is mononeuritis multiplex
Causes of generalised peripheral neuropathy (6)
Hereditary
Metabolic: diabetes, alcohol, renal failure, B12
Toxic: drugs
Infectious: Lyme, HIV, leprosy
Malignancy: paraneoplastic
Inflammatory demyelinating:
Acute = Guillain Barre syndrome
Chronic = chronic inflammatory demyelinating polyneuropathy
Nerve disease can be of which 3 types?
Root disease
Lesion of individual peripheral nerve
Generalised peripheral neuropathy
Symptom and signs:
Nerve root disease (3)
Myotomal wasting and weakness
Reflex change
Dermatomal sensory change
Symptom and signs: Individual nerve (2)
Wasting and weakness of innervated muscle
Specific sensory change
Symptom and signs:
Generalised peripheral neuropathy
Sensory and motor symptoms, usually starting distally and moving proximally
Investigations for nerve disease (5)
Blood tests
Genetic analysis
Nerve Conduction Studies
Lumbar puncture (CSF analysis) – invasive , not done much
Nerve biopsy (nb sensory nerve)
Treatment of nerve diseases?
Treat the cause eg stop drug, surgery, immunoglobulin
What is solely affected in spinal muscular atrophy?
anterior horn cell
Motor neuron disease:
Disease progression and signs
Usually starts with limb → bulbar → respiratory
combination of UMN and LMN signs LMN = muscle fasciculations, wasting, weakness UMN = increased tone, brisk reflexes No sensory involvement 10%+ have cognitive decline
Doesn’t affect sensory just the motor part
Prognosis of Motor Neuron disease?
Median 3-5 years from symptom onset
2-3 years from diagnosis
50% die within 14 months of diagnosis
What do you usually see in an atrophic tongue
fasciculations, wasting and weakness (LMN signs), while spasticity causes slow tongue movements
Treatment of motor neuron disease
Supportive - PEG feed, non invasive ventilation, physio, OT, SALT, care
Riluzole - delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months
Anticipatory / palliative care
Diagnosis of motor neuron disease
unique combination of UMN and LMN signs with no sensory signs
Electromyography
What is the presentation of disorders of the neuromuscular junction?
Fatiguable weakness:
–Limbs
–Eyelids (ptosis)
–Muscles of mastication (chewing), swallow
–Talking
–SOB - Affects all NMJ’s so can cause respiratory failure
–diplopia
Clear feature of NMJ problems is fatigue – muscles start strong and then get weaker. As day goes on – progressive problem with muscle weakness – diplopia because of muscle weakness in the eye.
Which antibodies are searched for in Myasthenia Gravis?
AChR, Anti MuSK antibodies
What is the other name for motor neuron disease?
Amyotrophic lateral sclerosis
