Transcript Approach to the Patient with Weakness

Approach to the Patient with
Weakness
What are clinical features that might
lead you to believe that weakness is
peripheral?
Why is it important to localize within
the peripheral nervous system?
Localization within the Peripheral
Nervous system
Peripheral Nerve/
Axon
Neuromuscular
Junction
Cell Body
Muscle
Weakness in Motor Neuron Disease
Distribution
Muscle Tone
Variable but asymmetric
at onset
Hypotonic/Flaccid*
Sensory Loss
No
Reflexes
Hyporeflexic*
Other Features
Atrophy, fasciculations,
cramping
* Amyotrophic lateral sclerosis (ALS) and some related disorders affect both the motor neuron
AND the corticospinal tracts, so patients have BOTH upper and lower motor neuron signs. In
addition to the above features, these patients may have spasticity and hyperreflexia.
Examples of Motor Neuron Disease
• Congenital
– Spinal Muscular Atrophy (SMA) - Types 1(most severe)-4(adult onset)
• Autosomal recessive: Survival motor neuron (SMN) gene (5q13)
• Amyotrophic Lateral Sclerosis
– Neurodegenerative disease affecting motor neurons of the anterior horn (LMN
signs) and the motor cortex (UMN signs)
– Sporadic (90-95%) and hereditary (5-10%)
• Most common genetic form is autosomal dominant
– Most common genes: C9ORF72 (9p21) and Superoxide dismutase (SOD) 1 (21q22)
• Infectious
– Poliovirus - Enterovirus eradicated in the U.S.
• Other enteroviruses can cause similar disease - Enterovirus 70 and 71
– West Nile - Mosquito borne flavivirus
• Post Radiation - Years after para-aortic radiation
Weakness in Peripheral Nerve Disease
Distribution
Distal > Proximal
Muscle Tone
Hypotonic
Sensory Loss
Yes
Reflexes
Hyporeflexic
Other Features
Distal atrophy over time,
paresthesias/pain
Examples of Peripheral Nerve Disease
•Trauma - Especially entrapment neuropathy
• Axonal
– Systemic illness
• DM, uremia, cirrhosis, SLE,
amyloidosis
– Toxic
• EtOH, heavy metals
• Meds - Chemo (platinum,
taxanes)
– Nutrition
• B12, folate, B6
– Infection
• HIV, Herpes, leprosy
• Demyelinating
– Hereditary
• Forms of Charcot-Marie
Tooth
– Guillian-Barre (AIDP)
• Preceding illness
– e.g. Campylobactor
• Ascending weakness
• No reflexes
– CIDP - Chronic form
– Infectious – CMV, Lyme,
Cryoglobulinemia, HIV,
Diptheria
Weakness in Neuromuscular Junction Disease
Distribution
Proximal>Distal, Bulbar
Muscle Tone
Normal
Sensory Loss
No
Reflexes
Normal to hypo, may
facilitate with repeat
testing
Fatigability
Other Features
Examples of Neuromuscular Junction
Disease
• Myasthenia Gravis
– Postsynaptic autoimmune disease
• Antibodies to ACh receptors or MuSK
– Sometimes associated with thymoma
• Lambert-Eaton Myasthenic Syndrome (LEMS)
– Presynaptic autoimmune disease
• Antibodies to voltage gated calcium channels
– Often associated with small cell lung cancer
• Botulism
• Toxic
– Organophosphates, curare, black widow venom, some snake
venom, aquatic neurotoxins (cone snail, stone fish)
Weakness in Muscle Disease
Distribution
Proximal > Distal
Muscle Tone
Normal
Sensory Loss
No
Reflexes
Normal
Other Features
Sometimes myalgia
Examples of Muscle Disease
• Hereditary
– Duchenne/Becker muscular dystrophy
• X-linked - Dystrophin gene
• Duchenne (more severe) - reading frame disrupted, Becker (less severe) reading frame preserved
– Mitochondrial disease
• Inflammatory
– Dermatomyositis
• Skin change - Gottron’s papules, heliotrope
• Higher incidence of malignancy
– Polymyositis
• Critical Illness Myopathy
• Toxic
– Statins, glucocorticoids
Peripheral Nervous System Weakness
Motor Neuron Peripheral
Nerve
Neuromuscular
Junction
Muscle
Distribution
Variable
Typically
Distal
Proximal, Bulbar
Proximal
Muscle Tone




Sensory Loss
No
Yes
No
No
Reflexes

 If

demyelinating May be facilitated
or severe
with repeat testing
axonal large
fiber

Paresthesias
Sometimes
myalgia
Other
Features
Fasciculations,
cramping
Fatiguability
May be
down if very
weak