NEURO - Neuromuscular diseases Flashcards
What are Neuromuscular Disorders? (what 3 things do they affect?)
Conditions that affect
a) Peripheral nervous system-motor and/or sensory nerves (includes anterior horn and dorsal root ganglion cell disorders )
b) Neuromuscular junction
c) Muscle
What are the Symptoms that may suggest a neuromuscular disease?
- Muscle Weakness /Wasting
- Sensory Loss/Numbness
- Fatigue
- Clumsiness
- Poor Balance/Falls
- Diplopia/Blurred Vision
- Dysphagia
- Dyspnoea
- Cramps
- Fasciculation
- Burning / Tingling
- Stiffness
Define & give (2) examples of focal neuromuscular disease
Weakness or sensory loss in the territory of a single nerve or nerve root
–Carpal tunnel syndrome-sensory symptoms affecting median nerve supplied digits (thumb, index & middle fingers)
–L5 radiculopathy or peroneal neuropathy causing unilateral foot drop
Discuss the distribution of generalised neuromuscular disease symptoms & signs
- motor
- sensory
MOTOR
- Proximal weakness: MYOPATHY, MYASTHENIA
- Distal Weakness- NEUROPATHY, MND (more often than proximal), Myopathy (rarely)
SENSORY
•Indicates a neuropathy-classic “glove & stocking loss”
– (excludes MND, MG or a myopathy)
(4) Examination findings of anterior horn cell/motor axon pathology (LMN lesion) on inspection
- Muscle Wasting (focal or generalised): Focal-root, nerve
- Fasciculations (Ant. Horn Cell, benign)
- Foot Drop/Wrist Drop
- Characteristic facies- Myotonic Dystrophy
(2) Examination findings of neuromuscular junction pathology on inspection
Ptosis, Strabismus (misalignment of the eyes)
(3) Examination findings of sensory pathology on inspection
Trophic changes of skin
Ulcers
Amputation of toes
(3) neuromuscular disease causes of diplopia & ptosis
- Myasthenia Gravis
- Ocular nerve palsy
- Thyroid eye disease
- NOT Motor neuron disease
(2) neuromuscular disease causes of dysphagia & dysarthria
- Myasthenia Gravis
* Motor neuron disease
Describe signs of anterior horn cell diseases
- muscle wasting
- fasciculations
- weakness
- reflexes
- sensation
- muscle wasting: early
- fasciculations: common
- weakness:diffuse, mixed picture
- reflexes: normal/increased
- sensation: normal
Describe signs of neuropathy
- muscle wasting
- fasciculations
- weakness
- reflexes
- sensation
- muscle wasting: late
- fasciculations: infrequent
- weakness:distal more than proximal
- reflexes: lost/absent early
- sensation: glove& stocking loss
Describe signs of myasthenia gravis
- muscle wasting
- fasciculations
- weakness
- reflexes
- sensation
- muscle wasting: no
- fasciculations: no
- weakness: proximal more than distal. Ptosis, eye muscles fatigues
- reflexes: normal
- sensation: normal
Describe signs of myopathy
- muscle wasting
- fasciculations
- weakness
- reflexes
- sensation
- muscle wasting: late
- fasciculations: no
- weakness: proximal more than distal
- reflexes: normal
- sensation: normal
(4) Ix if you suspect a neuromuscular problem
•A) Electrophysiology
–Distinguishes neuropathy from myopathy, axonal from demyelinating, sensory vs motor, NMJ Disorder
•B) Laboratory
–FBE, ESR, Vit B12, CXR, RBS, HbA1c, U&E,TFT, LFT, PEP, ANF, ANCA, ENA, HIV, CK, Heavy Metal screen , VDRL, Genetic Tests
•C) Lumbar Puncture
–Elevated protein , no cells in inflammatory demyelinating neuropathies eg GBS,CIDP
•D) Muscle Biopsy , Muscle MRI
–if suspect a myopathy
Reserved for difficult cases:
•E) Nerve Biopsy
•F) MRI of nerve
- 55 year old previously well building surveyor
- On no medications
- 6 months ago noticed cramps in both legs worse after exercise
- Increasing leg weakness over past 3 months with left foot drop.
- Had noticed twitching in the muscles of both legs.
- No sensory complaints
- No family history of weakness
- Cranial nerve examination normal. No tongue wasting or fasciculations
- Few scattered fasciculations in upper limb muscles (deltoid and periscapular)
- No muscle wasting or weakness
- Brisk reflexes
- No sensory loss
- Thin leg muscles , fasciculations in thighs only after exercise
- Weakness of hip flexion 4/5 and ankle dorsiflexion 3/5 bilaterally
- Reflexes brisk, plantars downgoing
- Normal sensation
- CK 859 (N: 50-200)
- NCS/EMG- Normal nerve conduction-motor and sensory nerves. Evidence of active and chronic denervation on needle EMG and fasciculations
DDx?
–Amyotrophic Lateral Sclerosis (ALS: most common motor neuron disease. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscle wasting. This results in difficulty speaking, swallowing, and eventually breathing.)
–Is a Disorder of Upper and Lower Motor Neurons
–Associated in some with Fronto-Temporal Dementia (FTLD)
- 35 year old previously well lawyer
- On no medications
- 6 months ago she noticed episodic diplopia, worse towards the end of the day
- Now increasing dyspnoea over past month with exercise
- No sensory complaints
- No family history of weakness
- Mild ptosis (L>R)
- Failure to fully adduct the left eye
- Speech becomes slurred during the latter part of history taking
- Proximal weakness in shoulder girdle muscles not evident initially but appears with repetitive trials
DDx?
Post-Synaptic
–Myasthenia Gravis: Post-Synaptic Abs vs Acetylcholine receptors
–MuSK Myasthenia: Post-Synaptic Abs vs MuSK
Pre-synaptic
–Lambert Eaton Myasthenic Syndrome (LEMS)
•Pre-Synaptic, Ab’s vs Ca2+ channels
•Often associated with neoplasm (50%) small cell lung
–Botulism
(6) Clinical Features that should make you suspect Myasthenia Gravis
- History of fatigueability
- Early involvement of extraocular muscles and lid opening muscles
- Dysarthria
- No muscle wasting
- Weakness increasing with repetitive exercise
- Reflexes and sensation unaffected
Pathogenesis of myasthenia gravis
- Due to autoantibodies which cross react with the acetylcholine receptor at neuromuscular junctions
- High association with thymic hyperplasia or thymoma
Pathogenesis of MuSK Myasthenia
Antibodies binding to MuSK (c.f. antibodies to ACh receptor) cause the subunits of the Ach Receptor to deaggregate and lose function
A subset of myasthenia gravis
(4) Diagnostic tests for myasthenia gravis
- Tensilon Test
•use short acting AChesterase antagonist -> increased ACh at the junction -> temporary reversed weakness in MG - Blood test for Autoantibodies-Ach Receptor, MuSK
- CT Chest- Thymoma
- EMG Studies- Rep Stim, Single Fibre EMG, Post-Exercise Facilitation
Pathogenesis of myasthenia gravis vs. Lambert-Eaton
Myasthenia gravis: Antibodies against AChR (post synaptic)
Lambert-Eaton: antibodies against presynaptic calcium channels. 50% associated with small cell lung cancer (pre-synaptic)
Compare eletrophysiology of myasthenia c.f. Lambert-Eaton
MG: Reduction in the amplitude of the muscle response with repetitive nerve stimulation (using up the ACh available)
C.f. Lambert-Eaton: changes to CMAP (compound muscle action potential) size post exercise
Difference b/w myasthenia gravis & Lambert-Eaton from repetitive movements (e.g. making a fist)
Myasthenia gravis: get gradually tired (using up ACh)
Lambert-Eaton: gets gradually stronger (mechanically open up the presynaptic Ca2+ channels)
- 65 year old Type II diabetic
- On no medications
- Complains of poor balance and feelings in soles of feet like “walking on cotton wool”
- Poor Balance on walking
- Wide based gait
- Romberg’s positive
- Weakness of dorsiflexion bilaterally
- Absent ankle reflexes
- Stocking loss of pain and temperature sensation with a level where it changes from abnormal to normal just below both knees
Basic causative pathology?
Neuropathy
Describe focal mononeuropathies
- (5) types of causes
- (2) Dx
Most common type of neuropathy
Symptoms consistent with anatomy of nerve involved
–Compressive: carpal tunnel syndrome, Ulnar Neuropathy
–Rarely other causes
•Infection: Leprosy
•Inflammatory: Eg: Bell’s Palsy
•Infiltrative: Cancer, amyloid
•Ischaemic: Eg: diabetes (III N palsy
Diagnosis
- Focal symptoms and signs
- NCS/EMG to localise lesion and confirm diagnosis
Describe multifocal mononeuropathies (mononeuritis multiplex)
- Px
- (2) types of causes
Multiple peripheral nerves affected rather than generalised
–eg ulnar and tibial
- Almost always ischaemic: Eg: diabetes, vasculitis
- Occasionally infective: Eg: AIDS, CMV, Sarcoid, leprosy
Describe generalised peripheral neuropathies
- chronology type
- pathology types
- most common system affected
•Acute or Chronic
•Axonal or Demyelinating
•Sensorimotor most common
–distal weakness and glove and stocking sensory loss
Px of acute polyneuropathies
- (3) examples of demyelinating
- (5) examples of axonal pathology
Rapidly increasing diffuse weakness &/or sensory loss occurring over days
•Demyelinating
–Guillain-Barre Syndrome
–AIDS-seroconversion phase
–Lymphoma
•Axonal
–AMAN (acute motor axonal neuropathy), AMSAN (acute motor sensory axonal neuropathy)
–Glue sniffers neuropathy: N-Hexane toxicity
–Vasculitis
–Thiamine Deficiency
–Porphyria
Causes of chronic polyneuropathies
- (7) causes of axonal pathology
- (3) causes of demyelinating pathology
Axonal –Genetic: HMSN Type II –Metabolic: Diabetes, Hypothyroidism –Toxin: Alcohol, Drugs, Prescription medication, Heavy Metals (As, Pb) –Nutritional: thiamine, B12 defc, B6 excess) –Paraneoplastic: Anti Hu –Immune: Abnormal paraprotein, Sjogren’s –Ischaemic: Diabetes, vasculitis
Demyelinating –Genetic: HMSN Type I, HNPP –Immune •Inflammatory: CIDP •Non-Inflammatory: IgM anti MAG –Paraneoplastic: POEMS
Classic changes on Motor nerve conduction studies (MNCS) for axonopathy
low amplitude CMAPs , normal conduction velocity
Classic changes on Motor nerve conduction studies (MNCS) for inherited demyelinating neuropathy
Slow conduction velocity, no block (C.f. conduction block in acquired)
Classic changes on Motor nerve conduction studies (MNCS) for acquired demyelinating neuropathy
Slow conduction velocity & conduction block (c.f. no block in inherited)
- 18 year old previously well young man
- History of increasing weakness over last 6 months
- Most noticeable getting out of chairs, walking up stairs, using hair dryer
- On no medications
- No sensory complaints
- Family history of weakness
- Does not fluctuate during day
- Waddling gait
- Can’t rise from squat without help
- Proximal weakness in shoulder girdle and hip girdle muscles
Basic causative pathology?
Myopathy
(4) pathologies of myopathies
- inherited (dystrophies; Duchenne’s, Becker’s, etc)
- metabolic
- ion channel mutations
- acquired (drugs, endocrine/metabolic, inflammatory)
(4) Ix of myopathies
- Electrophysiology: Needle EMG: myopathy, myotonia
- CK: if elevated almost always indicates a myopathy. (Occ: 500-1000 in MND)
•Family History- Genetic Tests
–Myotonic Dystrophy: Triplet Repeat Chr. 19
–Duchenne’s: Loss of Dystrophin gene on X chromosome
•Muscle Biopsy
(3) What would you see in muscle biopsy in muscular dystrophies?
- Varying muscle fibre size
- Regenerating and Degenerating fibres
- Increased fibrosis
What special stains could you use to identify muscle membrane proteins for Ix of muscular dystrophies?
- Duchenne’s, Becker’s
- Limb Girdle Dystrophies
- Limb Girdle Dystrophies
- Dystrophin- Duchenne’s, Becker’s
- Dysferlin- Limb Girdle Dystrophies
- Sarcoglycans-Limb Girdle Dystrophies
(2) What would you see in muscle biopsy in polymyositis?
•Inflammatory cell infiltrate
–T lymphocytes: Polymyositis and Inclusion body myositis
–B lymphocytes: Dermatomyositis
•Degenerating and regenerating muscle cells
