Neuromuscular Flashcards
Duchenne Muscular dystrophy (DMD)
• More severe
• 2-3 yrs age of onset
• Cardiomyopathy - develops over time
• Ortho Cx - frequent
• Wheelchair bound 13 yrs
• CK x 10-20 upper limit
Out of frame deletion
Becker Muscular dystrophy
• Less severe
• Age of onset 5-60
• Cardiomyopathy - prominent feature in presentation
• Wheelchair bound 16 yrs
• In frame deletions
• CK X 5 upper limit
• Retained strength
• Preservation neck flexor muscles
Reading frame hypothesis (DMD BMD)
• Out of frame deletion - very unstable, severely truncated dystrophin –> DMD more severe
• In frame deletion - preserves translational reading frame - semi functional dystrophin gene - BMD mild phenotype
Neuromuscular junction - explain normal physiology
Infantile botulism - how it effects, clin pres, Mx
• Action potential moves down nerve axon –> reaches synapse
• Release Ach into synapse
• Ach acts on membrane receptor on muscle membrane
• Influx of calcium and contraction
• Pre-synaptic, synaptic, post synaptic
Infantile botulism
• 3-4 months
• Clostridium botulinum (A & B)
• Neurotoxin blocks pre-synaptic release of Ach
• Honey, spores, home canned foods
Clin Pres
• Constipation, poor feeding
• Progressive descending hypotonia and weakness
• Cranial nerves (ptosis)
Ix - C botulinum spores in stool
EMG
Mx
• Botulism immunoglobulin (anti toxin)
Neonatal hypotonia “floppy infant”
- Central vs peripheral, common DDx and broadly how to differentiate
Floppy weak - no or reduced antigravity movements - neuromuscular, no reflexes, weak
Floppy strong -can move against gravity - central - reflexes present
Central (Central hypotonia)
• Floppy strong (move against gravity), normal/brisk reflexes
• HIE, infection, endocrine, genetic/syndrome - Prader Willi, T21, Fragile X
• Cerebral malformations
• Demyelination
• Spinal cord disorder
• Other Sx - dysmorphic, seizures, macro/microcephaly,
Peripheral
• Floppy weak - no or reduced antigravity movements, no reflexes
• Anterior horn - SMA, mimics mitochondrial disease
• Neuropathies
• Neuromuscular problems - transient autoimmune neonatal myaesthesia
• Muscle - congenital muscular dystrophies, congenital myopathies, metabolic myopathies eg Pompe, congenital myotonic dystrophy
Other Sx - fasciculations, ptosis, eye movements, FHx
Common DDx for neonatal hypotonia
Prader Willi - 15p deletion
• Severe hypotonia, feeding difficulty
• Chromosome 15 problem
• Obesity
Peripheral
SMA
• SMA 0 - severe neonatal hypotonia, early resp failure (need resp support since birth)
• SMA 1 - onset <6 months, variable suck/swallow
Neonatal myaesthenia grava
• Transient in mothers with MG - 10-20%
• Weakness, hypotonia
• Bulbar - poor suck swallow
• Pool secretions
Myotonic dystrophy
• Myotonia - can’t relax muscles
• Congenital
Charcot Marie Tooth (Hereditary Motor-Sensory Neuropathy)
Key 3
• Most common genetically determined neuropathy
• Chronic motor and sensory polyneuropathy
• Key features - muscle weakness and wasting, distal > proximal, decreased reflexes, foot deformity, decreased distal sensation, motor and sensory neuropathy on NCS, wide variation in age of onset
Cause
• Mutations in gene making proteins expressed in myelin and axons
Classification
CMT Type 1 - Demyelination
• Demyelinating - NCV low - CMT1, 3, 4
• 1st/2nd decade
CMT Type 2 - Axonal
• Axonal - NCV > 38
• 2nd/3rd decade of life
• Mode of inheritance - AD CMT1, 2, 3, AR 4, X linked
Clin Pres
• Late childhood-adolescence
• Slow progressive
• Motor - peroneal and tibial earliest, most severely affected, difficulty walking, toe walking, clumsy hands, atrophy–> falls, weakness, clumsy
• Foot deformities - pes canus, pes planus
• Sensory –> injuries, ulcers
• Autonomic
• Pain
Ex
• Atrophy - muscles of anterior comp lower leg
• Progressive waekness - dorsiflexion - foot drop
• Bilateral, slight asymmetry
Ix
• NCS - motor and sensory velocities greatly reduced
• CK normal
• Muscle biopsy - not normally needed
• Genetics
Mx
• AFOs, surgical, prevent secondary Cx
• Nil medical Tx to slow progression
Guillian Barre
Key 3
• Acute inflammatory polyneuropathy - weakness, areflexia
• Secondary to infections - (GIT campylobacter jejuni, H pylori, resp - mycoplasma pneumoniae) r vaccines
• IVIG
• Acute inflammatory polyneuropathy • Rapidly progressive symmetric weakness and areflexia • CN involvement • Acute flaccid paralysis
Cause
• Infection or vaccination
• Infections - GIT campylobacter jejuni, H pylori
• Resp - mycoplasma pneumoniae
• Vaccines - rabies, influenza, polio, meningococcal C
Clin Pres
• Gradual, progressive, days to weeks up to 1 month
• Max severity of weakness by week
• LL –> UL, proximal, symmetrical
• CN common - facial weaknesss, bulbar weakness
• Loss of reflexes
Ix
• WCC <10, high protein > 0.45 (cytoalbuminological dissociation)
• NCS - demyelinating vs axonal (slow vs normal)
• MRI
• Stool - exclude polio, campylobacter, VIDRL
• Path - anti GM1 - campylobacter assoc GBS, anti GQ1b–> Miller Fisher syndrome
Mx
• Resp support
• Neuropathic pain
• IVIG - 2g/kg
Outcomes
• Better than adults
90% fully recover, relapses uncommon, very small % develop CIDP
Chronic inflammatory demyelinating polyneuropathy
• GBS that lasts > 8 weeks
• Symmetrical proximal and distal muscle weakness
• Areflexia
• Cranial nerve and bulbar in 10-20%
• NCS - demyelinating (slow conduction)
• Relapsing/remitting course
Slowed conduction
Myotonic dystrophy
Key 3
• Myotonia - slow muscle relaxation after contraction
• Triplet repeat expansion - CTG repeat in gene
• Congenital - most severe, resp failure and early death common,
Facial wasting prominent
Congenital Myopathies
• Primary muscle disorders - present since birth
• Muscle biopsy - diagnostic, CK normal
Central core disease -ryanodine (RYR1), Nemaline myopathy - most common, sever congenital forms
Myasthenia gravis
Neonatal MG
• NMJ
• Autoimmune resulting in neuromuscular blockade –> rapid fatiguability
• Antibodies to ACH receptors
• Rapid fatiguability of muscles
• Ptosis
• CN involvement
• Myasthenic crisis - acute weakness in pt with MG
Ix
• Anti-AChR
• Anti Musk
• NCS - electro-decremental response
Mx
• Immunotherapy
• Anti-cholinesterase medications - neostigmine, pyridostigmine
Neonatal myaesthenia gravis
• Transient in mothers with MG - 10-20%
• Weakness, hypotonia
• Bulbar - poor suck swallow
Pool secretions
What expect on NCS for GBS?
Slowing of motor and sensory nerve conduction with evidence of conduction block
Nursinerson - which gene
SMN2 gene
Ticks - MOA of paralysis?
decrease neurotransmitter release
