Muscle & Nerve Disease Flashcards
Think about the way muscle diseases can present in a patient
Symptoms [5]
Signs [3]
- Weakness
- SOB from resp muscles
- Poor swallowing or aspiration
- Cardiomyopathy
- Cramp, pain, myoglobinuria
- Wasting or hypertrophy
- Reduced tone & reflexes
- Motor Weakness
What is myoglobinuria? [2]
Myoglobin leaked from muscles that are breaking down due to certain muscle diseases. [1]
It’ll appear after exercise as black urine [1]
List the classifications of muscle disorders? [6]
- Dystrophies
- Chanellopathies
(ion channel problems -> unrelaxable or weak muscles) - Metabolic muscle diseases
- Inflammatory muscle diseases
- Congenital Myopathies
- Iatrogenic
Drug induced muscle disease
Causes
LSD CHAP
- Lipid lowering agents, e.g. statins, fibrates, nicotinic acid, ezetimibe.
- Steroids.
- Drugs of abuse, e.g. alcohol, heroin, cocaine.
- Colchicine, chloroquine.
- Hydroxychloroquine.
- Amiodarone.
- Perhexiline.
Causes of raised CK [4]
General marker for muscle damage
■ Intense periods of exercise.
■ Rhabdomyolysis following prolonged immobilisation.
■ Denervation.
■ Drug ingestion (especially statins).
■ Muscle disease
What investigations are common for muscular diseases? [5]
- Creatine Kinase
- Lactate
- Ammonia
- Electromyography to distinguish between deneravation, NMJ disorders and primary muscle disease.
- Biopsy is crucial with enzymic stains and IHC.
- Genetic Tests (Most muscular dystrophies are genetic)
List some muscular dystrophies? [3]
- Duchenne’s MD & Becker’s MD
- Facioscapulohumeral
- Limb Girdle MD (Proximal limb weakness)
- Emery Dreifuss MD
Give one example of a channelopathy and describe it [3]
Familial Hypokalemic Periodic Paralysis [1] causes episodes of sudden muscle weakness [1] lasting seconds -> days [1]
Give an example of a metabolic muscle disease [1]
Endocrinopathies such as Thyroid or Cushing’s disease can affect the muscles.
Inflammatory muscle disease
Split causes into pathophysiology [4]
- Idiopathic myositis - polymyositis, dermatomyositis
- Autoimmune-associated myositis - SLE, RA, Mixed CTS, Sjogrens
- Infection associated myositis- viral, bacterial, parasitic
- Other diseases associated with myositis - vasculitis, sarcoidosis
What is myasthenia gravis? [2]
Describe its key feature [3]
What can this key feature manifest as? [4]
Autoimmune disorder [1] resulting in insufficient functioning acetylcholine receptors. [1]
The key feature is muscle fatigability[1] - muscles become progressively weaker during periods of activity [1] and slowly improve after periods of rest [1]
extraocular muscle weakness:
1. diplopia
2. proximal muscle weakness: face, neck, limb girdle
3. ptosis
4. dysphagia
What causes myasthenia gravis? [2]
What is it associated with? [3]
An auto-antibody blocks ACh receptors in the NMJ. [1]
Its fatigable because early in the day you produce lots of ACh so it can compete with the antibody [1] but by the end of the day its depleted and the antibody wins out so you get weaker until you rest again [1]
Associations
- thymomas in 15%
- autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
- thymic hyperplasia in 50-70%
What investigations can you do for Myasthenia Gravis? [5]
- AutoAntibody Tests
70% +ve, 40% positive for anti-MUSK abs - CT chest to exclude a thymoma
- Electromyography
- Tensilon test
How does an EMG test for Myasthenia Gravis? [2]
Explain how the Tensilon test is done [1]
Repetitive stimulation should make the muscle fatigue, evident as a reduced amplitude on an EMG.
Tensilon test
- IV edrophonium reduces muscle weakness temporarily
MG Tx [3]
Management of myasthenia crisis [2]
- Acetlycholinesterase Inhibitors eg pyridostigmine
- Immunosuppression prevents antibody production (Prednisolone or Azathioprine), high dose steroids may cause initial deterioration
- Thymectomy can prevent antibody production, early intervention against future thymoma?
Management of myasthenia crisis:
- Plasmapheresis
- IvIg
Define Peripheral Neuropathy?
Damage to nerves outside the CNS.
It can affect sensory axons, motor axons and ANS fibres
Can either be disease of a spinal root, single peripheral nerve or generalised peripheral neuropathy
What could cause a lesion to a single peripheral nerve?
- Compression or entrapment
- Vasculitis to the vessels supplying the nerve
What could cause generalised peripheral neuropathy? [6]
Metabolic: DM, alcohol Toxic Drugs Infections e.g. HIV Inherited Paraneoplastic (e.g. prostate) Inflammatory demyelinating such as Guillain barre (acute) or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) B12 deficiency
Define Guillain Barre Syndrome [3]
Describe 3 key features
Immune mediated [1] demyelination of the peripheral nervous system [1] often triggered by an infection
(because the viral antigen is very similar to myelin) [1]
Causes rapid onset muscle weakness/wasting (ascending), areflexia and sensory changes
around 65% of patients experience back/leg pain in the initial stages of the illness
What tests can be done for peripheral neuropathies? [5]
- Blood Tests (particularly for inflammatory conditions)
- Genetic Analysis
- Nerve Conduction Studies e.g. EMG
- Lumbar Puncture for CSF analysis
- Nerve Biopsy
What is the main type of anterior horn cell disorder? [1]
Motor Neuron Disease (Amyotrophic Lateral Sclerosis - ALS)
Its a progressive loss of motor neurons (Upper & Lower)
How does ALS present? [6]
Mixed upper and lower motor neuron signs: # LMN - Fasciculations, Wasting, weakness # UMN - Increased Tone, Hyperreflexia # Theres no sensory involvement # No ocular or sphincter involvement
- Frontotemporal dementia
- Stumbling spastic gait, foot drop
- Weak grip, weak shoulder abduction
Whats the prognosis for Motor Neuron Disease? [1]
3 yrs median survival post-diagnosis
how do we diagnose ALS? [2]
Electromyography [1] showing denervation changes in >3 body regions [1]
How would you treat ALS? [5]
Supportive treatment:
- PEG Tube
- Drooling: PROPANTHELINE or AMITRYPTILINE
- Spasticity: baclofen
- Respiratory failure: NIV
- Physiotherapy, OT
Also Riluzole:
- Licensed for improving lifespan in ALS 3m
SE: LFTs increased, vomiting, tachycardia, somnolence, headache, vertigo
What is Lambert-Eaton myasthenia syndrome?
What is its key feature [1]
Caused by antibody directed against presynaptic voltage gated calcium channel in the PNS
Associated with underlying malignancy SCLC 75%
Repeated muscle contractions lead to increased muscle strength
Lambert Eaton Syndrome
What is this condition associated with? [1]
Describe 4 other symptoms
Has an association with small cell lung cancer
Other symptoms:
limb-girdle weakness (affects lower limbs first)
hyporeflexia
autonomic symptoms: dry mouth, impotence, difficulty micturating
ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
Describe the causative organisms that can trigger GBS [4]
- Most common Campylobacter jejuni (GE infections)
- Mycoplasma pneuonia
- Haemophilus influenza
- CMV, HIV
What is Miller Fisher syndrome [3]
Associated with ophthalmoplegia, areflexia and ataxia
Miller Fisher syndrome
- Difference between GBS? [1]
- What antibodies are found in 90% of cases? [1]
Usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome
Anti-GQ1b antibodies
GBS
Symptoms [5]
- Progressive ascending muscle weakness up to 4w after trigger
- Proximal muscles > distal so respiratory, CN VII affected
- Deep tendon jerks are typically lost
- Back and limb pain
- Sensory disturbance
- Autonomic dysfunction: sweating, tachycardia, BP changes
GBS diagnostic criteria (and signs) [7]
Investigations [2]
- Progressive weakness of all 4 limbs and areflexia is needed for dx
- Progression over days
- Near symmetry of symptoms
- Sensory features are mild
- CN involvement e.g. bilateral facial weakness
- Recovery starts 2w after period of progression finished
- Absence of fever at onset
Investigations
- CSF protein increased, CSF WCC low
- EMG showing slow conduction
Chronic inflamamtroy demyelinating polyneuropathy
Antibody mediated inflammation results in segmental demyelination of peripheral nerves
* Similar to GBS but more insidious onset over weeks to months
* CSF has high protein content
GBS Tx [3]
Tx: plasmapheresis, immunoglobulin, artificial ventilation
Charcot marie tooth syndrome
AKA
Ax
Px [2]
HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE I
Ax:
- autosomal dominant (but some X-linked varieties)
Px:
- neuronal degeneration of genes that
- code the proteins involved in structure or function of nerve axons or myelin sheaths
Charcot marie tooth syndrome
Presentation [4]
- onset at puberty with peroneal atrophy
- causing leg weakness, foot drop and variable loss of sensation
- champagne bottle leg appearance (peroneal atrophy)
- foot deformity (high arches and hammer toes)
CMT syndrome
Ix [3]
Mx [4]
Prognosis
Ix: EMG, nerve biopsy, genetic testing excl. other causes of neuropathy
Mx: physio, OT, orthotics, analgesia
Pro: normal life expectancy
Autonomic neuropathy
Classification [2]
Primary:
- Autoimmune autonomic ganglionopathy
- Parkinsonian syndromes
Secondary causes
Secondary causes of autonomic neuropathy [8]
- DM
- amyloidosis
- Guillain Barre
- Sjogren’s, SLE
- HIV, leprosy
- Toxins
- porphyria
- paraneoplastic
Autonomic neuropathy: Presentation [7]
- Sympathetic failure:
1. postural hypotension (fainting on standing/eating/hot bath)
2. reduced sweating - Parasympathetic failure:
1. constipation
2. nocturnal diarrhea
3. urinary retention
Autonomic neuropathy: investigation [4]
- Confirm postural hypotension with lying/standing BP
- ECG shwoing variation of >10bpm with respiration is abnormal
- Cystometry, bladder pressure studies
- Pupil tests
What is motor neuron disease?
Selective loss of motor neurons in the motor cortex, cranial nerve nuclei and anterior horn cells
BUT NO sensory loss or sphincter disturbance (ddx from polyneuropathy/MS)
NEVER affects eye movements
Classification of MND
- ALS
- Progressive bulbar palsy: fastest progressing; only affects CN IX to XII
- Progressive muscular atrophy
- Primary lateral sclerosis
Progressive muscular atrophy [3]
- anterior horn cell lesion only
- so NO UMN signs
- affects DISTAL before proximal and better prognosis than ALS
Primary lateral sclerosis [4]
- loss of Betz cells in motor cortex
- causes mainly UMN signs
- with marked spastic leg weakness and pseudobulbar palsy
- no cognitive decline
Myotonic dystrophy
Inheritance pattern
Ax:
- autosomal dominant Cl- channelopathy (DM1 = chromosome 9, DM2 = chromosome 3)
- Genetics: anticipation (CTG repeats increase causing increasing severity with each generation)
Myotonic dystrophy
Onset
Presentation [3]
Non-neurological symptoms [7]
- onset at 25y/o w/ distal onset weakness (hand or foot drop)
- weak sternomastoid and myotonia (tonic muscle spasm)
- facial weakness and muscle wasting giving haggard appearance
- bilateral late onset cataracts
- male frontal baldness
- DM
- testis or ovary atrophy
- cardiomyopathy, heart block, post-anaesthetic death
- reduced cognition
Myotonic dystrophy mx [6]
- Genetic counselling
- Mexiletine
- Phenytoin
- Acetazolamide
- NIV for sleep apnoea
- Cardiac pacing (heart block)
Muscular dystrophies
Define
Hx and signs
Ix
Tx
- Genetic abnormality affecting muscle protein components.
- Hx/Exam: Gowers sign, progressive muscular wasting, waddling gait, calf muscle pseudohypertrophy, scoliosis, respiratory and cardio complications
- Ix: muscle biopsy, increased CK, EMG, Genetics
- Supportive treatment with no curative therapies.
What is XP21 dystrophy
x-linked recessive conditions
mutation of dystrophin gene at locus Xp21
Muscle fiber necrosis, replaced with adipose and connective tissue
Duchenne muscular dystrophy
Becker muscular dystrophy- reduced severity of phenotype
MuSK - what is the pathophysiology behind anti-MUSK antibiotics involved in Myasthenia Gravis?
Muscle specific kinase - tyrosine kinase receptor expressed selectively in skeletal muscles that helps to cluster post-synpatic proteins. Anti-MuSK abs may active complement inducing lysis of the post-synaptic membrane
Guillian Barre syndrome
Pathophysiology [2]
- Immune responses to ganglioside-like epitopes on the surface of triggering infectious agents cross- react with gangliosides displayed on nerve cells
- resulting in macrophage-mediated attack of either the Schwann cell or the axolemma.
