Muscle and Nerve disease Flashcards
What neurotransmitter is released at the neuromuscular junction?
Acetyl-choline (ACh)
Binds to the ACh receptor
What are the typical symptoms for a patient with muscle disease?
Symptoms:
- SOB/Dyspnoea - due to weakness of respiratory muscles
- Dysphagia/Aspiration - weakness of bulbar muscles
- Cardiomyopathy
- Cramp, pain, stiffness
- Myoglobulinuria
What typical signs are present with muscle disease?
- Wasting / Hypertrophy:
- Inspection of patient
- Normal or reduced tone and reflexes
- Motor weakness - but not Sensory weakness:
- Tests such as pinprick test will be normal
- Tests of power etc will show weakness
How would you investigate a patient with possible muscle disease?
History and Examination
Creatine Kinase (CK) - marker of muscle breakdown & damage. Also used for MI, acute Kidney injuries etc
EMG - Electromyography
Muscle biopsy
Genetic testing
Why is Electromyography a useful investigation for Muscle disease?
Effective at evaluating and recording the electrical activity produced by skeletal muscles
Will measure the action potentials produced by motor neurones
What information is gained from taking a muscle biopsy?
Structure
Biochemistry
Inflammation
What aspects of muscle function can be affected in congenital/genetic muscle diseases?
Structural - Muscular dystrophies
Contractile - Congenital myopathies
Coupling - Channelopathies
Energy - Abnormalities of enzymes/mitochondria
What are the 4 main categories of acquired muscle diseases?
Metabolic - Involving Ca2+, K+
Endocrine - Thyroid, adrenal, Vitamin D
Inflammatory muscle disease
Iatrogenic - from medications such as steroids, statins
What are muscular dystrophies?
A group of Inherited muscle diseases in which there is increasing weakening and breakdown of skeletal muscles over time
There is no cure for MD thus treatment is therapy is generally aimed at improving quality of life
In muscular dystrophies - what causes the muscles to weaken and atrophy?
Normally - the dystrophin protein links intracellular actin to the DAP complex in the cell membrane. The DAP is in turn linked to the extracellular matrix. This is to stabilize the sarcolemma.
In MD - no/abnormal dystrophin protein - no support - everything wilts and sarcolemma breaks. This allows Creatine Kinase to escape from the cell and Ca2+ entry to cells
Contrast the short-term and long-term effects on the muscle in muscular dystrophies such as DMD
In the short term:
- Muscle regeneration takes place to try and combat the cell death
- This leads to Some fibres becoming very large compared to others - giving a varied size of muscle fibres
In the Long term:
- Muscle atrophies
- Infiltration of fat and fibrotic tissue
Identify the labels in this diagram of the dystrophin-associated protein complex and all that stuff
What patients are most likely to have muscular dystrophies?
Younger or older onset
More common in males (although depends on specific type of MD)
What are the main types of Muscular dystrophy?
Dystrophinopathies - mutation of dystrophin gene:
- Duchenne’s (DMD) - most common
- Becker’s (BMD)
Other:
- Facioscapulohumeral MD
- Oculopharyngeal MD
- Limb girdle MD
- Myotonic dystrophy (cataracts)
What presentation is typical to:
A) Facioscapulahumeral MD
B) Oculopharyngeal MD
C) Limb-girdle MD
A) Develops at young age - weakness in skeletal muscles of face, scapula and upper arms
B) Adult onset - Weakness of upper eyelids & throat. Presents with ptosis & dysphagia
C) Any age - Weakness of skeletal muscles of arms & legs
What are channelopathies and how do they present?
Disorders of Ca2+, Na+, K+ & Cl- channels
Often paroxysmal symptoms - eg periodic paralysis / myotonia (delayed relaxation after contraction)
Partially treatable
Describe what a metabolic myopathy is
Disorders corresponding to energy production - characterized by mitochondrial problems
Exercise-induced:
- Early = disorders of carbohydrate metabolism
- Late = disorders of lipid metabolism
Partially treatable
What are the 2 main types of inflammatory myopathies (myositis) and their basic differences?
Polymyositis & Dermatomyositis (DM)
Polymyositis causes muscle weakness, usually in the muscles closest to the trunk of your body. Dermatomyositis causes muscle weakness, plus a characteristic skin rash.
In essence: Dermatomyositis = Polymyositis (muscle involvement) + skin involvement
What are the causes of Myositis?
(DM & PolyM)
Can be primary (of unknown aetiology) or secondary to autoimmune rheumatic disease or malignancy
What are the symptoms of Dermatomyositis and polymyositis?
Progressive proximal muscle weakness
Myalgia
Dysphagia
SOB
What are the signs of Dermatomyositis?
Periorbital oedema
Heliotrope rash
Gottron’s papules - scaley lesions on dorsum of hand
What investigations are done for dermatomyositis and polymyositis?
Elevated Creatine Kinase
Autoantibodies - check for Autoimmune rheum. D
Tumour screen - check for malignancy as cause. Especially important for DM
EMG
Muscle Biopsy
Why is biopsy useful to differentiate between Dermatomyositis & polymyositis
Polymyositis –> CD8 cells
Dermatomyositis –> humeral-mediated, B cells and CD4 cells
How are dermatomyositis and polymyositis treated?
Immunosuppression - Azathioprine/methotrexate
High dose Glucocorticoids
What is myasthenia gravis?
Autoimmune condition in which antibodies are directed against acetylcholine receptors on the postsynaptic muscle membrane
Linked to thyroid dysfunction
How does Myasthenia gravis present?
Weakness and fatiguability
Often affects cranial nerves early-on causing Ptosis of eyelids, Diplopia, dysphagia, dysarthria
Breathing difficulty
How is myasthenia gravis investigated?
ACh receptor antibodies
Anti-MusK antibodies
CXR/CT for thymus - thymoma
Neurophysiology tests - Repetitive stimulation, jitter
How is Myasthenia gravis managed?
Acetylcholinesterase inhibitor - pyridostigmine
- aka anticholinesterases
- Symptomatic treatment
Immunosuppression
- Steroid - Prednisolone
- Steroid saving agent - Azathioprine
Emergency situations:
- IV Immunoglobulins
- Plasma exchange - Plasmapheresis
What surgery can be done for Myasthenia gravis?
Thymectomy
What are the contents of peripheral nerves?
Sensory axons:
- Small fibres - pain + temperature
- Large fibres - touch + joint position etc
Motor axons
Autonomic axons
Nerve sheath (myelin)
What are the types of (generalised) Peripheral neuropathy?
Motor / Sensory / Motorsensory
+/- Autonomic features
What causes Sensory neuropathy?
Diabetes
Alcohol
Rheumatoid arthritis
Drugs
Malignancy
B12 Deficiency
Chronic renal failure
What causes General peripheral neuropathy?
Hereditary conditions:
- Charcot-Marie-Tooth disease
Guillain-Barre syndrome:
- Acute
- Autoimmune inflammatory response causing demyelination
Chronic inflammatory demyelinating polyneuropathy
Lead toxicity, drug toxicity
Infection - Lyme, HIV, Leprosy
Malignancy, renal failure
What are the signs of a nerve root disease?
Myotomal wasting & weakness
Reflex change
Dermatomal sensory change
What are the signs of individual nerve disease?
Wasting & weakness of innervated muscle
Specific sensory change
What are the signs of generalised peripheral neuropathy?
Sensory and motor symptoms, usually starting distally and moving proximally
How are nerve diseases investigated?
Blood tests - glucose, FBC, B12 levels
Genetic analysis
Nerve conduction studies
Lumbar puncture - CSF analysis
Nerve biopsy (nb sensory nerve)
Urine dipstick
History of alcohol consumption
How are nerve diseases treated?
Treatment aimed at cause for example:
Stop drug
Surgery
Immunoglobulins if underlying condition such as GB syndrome
What is the main disease of anterior horn cells (ie motor neuron that starts in horn)
Motor-neuron disease
(Amyotrophic Lateral Sclerosis)
What is motor neuron disease?
Degeneration of upper and lower motor neurones - of unknown cause
Male > female
typically 40-60 years old
Mostly Sporadic - but some are genetic
In what ways/stages can Motor-neuron disease present?
Spinal muscular atrophy (LMN?):
- Limb weakness, atrophy, fasciculations - due to involvement of spinal cord anterior horn cells
Primary lateral sclerosis:
- Spastic limb weakness due to UMN involvement of UMN
Progressive bulbar palsy:
- Bulbar symptoms (dysphagia?) due to involvement of bulbar motor neurones
Amyotrophic lateral sclerosis (ALS):
- All 3 of the above
What signs on examination would rule out Motor-neuron disease and ALS?
Any sensory investigation should give normal results as there is no sensory involvement
So any negative pin-prick test etc
What is the prognosis for Motor neurone disease (& ALS)?
Median 3-5 years from symptom onset, 2-3 years from diagnosis
50% die within 14 months of diagnosis
How is motor neuron disease investigated?
History
Examination showing UMN+/-LMN signs with no sensory signs
EMG - fasciculations & fibrillations
How is motor neurone disease treated?
Antispasmodics - eg baclofen
Glutamate antagonists - eg riluzole
Supportive - PEG feed, non invasive ventilation, physio, OT, SALT, care
Anticipatory/palliative care
