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Lecture 10: Acute and Chronic Peripheral Neuropathy
Timothy Beer (modified by David Reilly 2013)
Background
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Peripheral Neuromuscular System
o Motor Components
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Anterior horn cells (motor neurons) and its axons (motor nerves)
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Neuromuscular junction
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Muscle
o Sensory Components
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Peripheral sensory receptors
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Sensory nerves
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Dorsal root ganglion
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Spinal root
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Dorsal column of spinal cord
General Neuromuscular Signs and Symptoms
o Muscular
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Symptoms
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Weakness
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Fatigability
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Muscle cramps
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Muscle twitching
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Signs
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Weakness
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Atrophy
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Fasciculations
o Sensory
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Symptoms
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Numbness
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Tingling and other paresthesias
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Pain
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Signs
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Abnormal sensation to touch, pinprick, temperature, vibration, proprioception (joint position)
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Romberg sign (note that it does NOT distinguish central from peripheral)
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Skin changes (hair loss, color changes, temperature changes)
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Dysautonomia (orthostatic hypotension, cardiac arrhythmia, abnormal platelets, erectile or ejaculatory dysfunction)
The Motor Unit
o Components
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Anterior horn cell: lower motor neuron in the spinal cord
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Motor nerves: axons originating from the anterior horn cell
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Neuromuscular junctions: synapses between motor nerve axons and the muscle membranes)
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Muscles: myofibers innervated by motor nerve axons
o Principle of Sprouting and Motor Unit Size and The Relationship to Neuromuscular Junction and Muscle Disease
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Let anterior horn cell A be AHC1 and neighboring anterior horn cell B be AHC2
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If AHC1 dies, muscle may receive collateral sprouts from AHC2
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In this case, AHC2’s motor unit increases in size, by providing innervation to all muscle fibers previously connected to AHC1
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This process can occur in cases of peripheral motor nerve injury
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However, in neuromuscular junction and muscle disease, the unit size is NOT increased (i.e. no collateral sprouting)
MRC Muscle Power Scale
o 0: no contraction
o 1: flicker or trace contraction
o 2: active movement, but not against gravity
o 3: active movement against gravity, but not against resistance
o 4: active movement against gravity and some resistance
o 5: normal power
Electrodiagnostic Tests
o Nerve Conduction Studies (NCS)
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Assess several extraphysiologic aspects of large nerve fibers: amplitude, latency, duration and conduction velocity
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May help diagnose a neuropathy or radiculopathy, but results can be normal in myopathies
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Deliver mild, brief electrical charges (“shocks”), usually lasting 0.1 ms
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Capture electrical signals at distant spot from the stimulation site, after the signals have traveled through a motor or sensory nerve
o Needle Electromyography (EMG)
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Assesses motor unit function by evaluating the connection between the nerve and muscle, as well as intrinsic muscle function
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It is commonly preceded by nerve conduction studies (NCS) and the combination of EMG and NCS are often referred to as “EMG”
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Very fine needle is inserted into a given muscle and it functions as an electrode, capturing electrical signals from the tested muscle
Motor Neuron Diseases
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Amyotrophic Lateral Sclerosis (ALS): progressive degeneration of both upper AND lower motor neurons due to death of anterior horn cells
o Clinical Features
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Lower motor neuron findings include:
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Muscle twitching or fasciculations
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Weakness
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Limb and tongue atrophy
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Dysphagia
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Dysarthria
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Upper motor neuron findings include:
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Hyperreflexia
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Increased gag reflex
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Babinski sign
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Normal extraocular muscle and chewing muscle function
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Normal sensory function
o Management
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Riluzole
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Non-invasive ventilation (prolongs survival)
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Supportive care
o Epidemiology
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Typically sporadic (90%) but occasionally familial due to SOD-1 mutation (10%)
Werdnig-Hoffman Syndrome / Floppy Baby Syndrome (Spinal Muscular Atrophy Type 1): disease of the lower motor neurons
o Etiology
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Deletion of one of the two copies of the Survival Motor Neuron 1 gene (SMN-1)
o Clinical Features
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Areflexia
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Isolated tongue fasciculations
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Normal IQ
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Normal sensory function
o Management
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Supportive
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Prognosis depends on ventilatory status
o Epidemiology
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Autosomal recessive
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Presents between birth and 6 months (although there are adolescent and adult types, which weren’t expanded on)
Spinobulbar Muscular Atrophy (Kennedy Disease): defects in androgen receptor resulting in muscular deficits and other manifestations
o Etiology
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Defective androgen receptor (CAG repeat expansion)
o Clinical Features
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Muscle cramps
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Fasciculations
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Limb weakness
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Dysphagia
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Dysarthria
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+/- Gynecomastia
o Management
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Very slowly progressive disease
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NORMAL lifespan
o Epidemiology
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X-linked (so occurs in males)
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Anticipation phenomenon (like many CAG-repeat expansion diseases)
Peripheral Neuropathy
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General Characteristics of Peripheral Neuropathy
o Weakness: distal weakness more than proximal weakness (except in GBS)
o Tendon reflexes: reduced or absent
o Atrophy: distal muscles atrophy before proximal muscles
o Sensory: reduced sensation to both small fiber (touch, pinprick, temperature) and large nerve fiber (vibratory, proprioception) modalities
Etiologies of Peripheral Neuropathy (DANG-THE-RAPIST)
o Diabetes, Alcohol, Nutritional, GBS
o Trauma, Hereditary, Environmental toxins
o Rheumatologic, Amyloid, Paraneoplastic, Infectious, Systemic disease, Tumor
Patterns of Peripheral Neuropathy
o Distal Symmetric Polyneuropathy (stocking-and-glove)
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Length-dependent sensory loss (more deficits distally)
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Diabetes is the most common cause (other causes include hypothyroidism, alcohol, chemotherapy, vitamin B12 deficiency)
Mononeuropathy
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Single nerve
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Include nerve entrapment neuropathies (e.g. carpal tunnel syndrome)
Multiple Mononeuropathies
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Multiple nerves, asymmetric
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Associated with nerve infarction or inflammation (vasculitis-related neuropathies)
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Examples include lupus and polyarteritis nodosa (in actuality, diabetes is by far the most common cause of this)
Autonomic Neuropathies
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Postural hypotension, abnormal HR variability, GI dysmotility, erectile dysfunction, urinary detention (detrusor dysfunction)
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Can be associated with amyloid neuropathy and diabetic neuropathy
Small Fiber Sensory Neuropathy
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Characterized by numbness, paresthesias, burning pain
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Length-dependent pattern (distal deficits)
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EMG and NCS will be normal, because they only test for large nerve fibers
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Diagnosis may be confirmed by epidermal nerve fiber density assessment of a skin biopsy
Charcot-Marie-Tooth Disease (Hereditary Motor and Sensory Neuropathy)
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Etiology
o Duplication or mutation of PMP-22 (most common subtype - CMT1A)
Pathophysiology
o Disturbances of peripheral myelin  uniform demyelination
Clinical Features
o Distal > proximal
o Weakness
o Atrophy
o Numbness
Electrodiagnostics
o NCS: homogenously reduced conduction velocities
Epidemiology
o Autosomal dominant (although there are less common x-linked and autosomal recessive forms)
o The most common inherited neurological disorder
Patterns of Peripheral Nerve Damage
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Lesion of the neuronal cell body  death of the neuron, axon and dendrites
o Motor neuron (AHC) death: ALS
o Sensory neuron (DRG) death: Sjogren’s, anti-Hu paraneoplastic syndrome
Injury to axon  progressive death of axon distal to the injury site (Wallerian degeneration)
Injury to myelin  segmental demyelination
o Immune-mediated injury of myelin in peripheral nerves: GBS, CIDP
Guillain-Barré Syndrome (GBS)
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Etiology
o Acquired autoimmune acute demyelinating disorder most commonly following viral or bacterial infection or vaccination
Clinical Features
o Motor
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Ascending weakness of the lower and upper limbs, beginning distally
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Risk of progression to quadriplegia and respiratory dysfunction, requiring ventilator until recovery (< 4 weeks)
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Areflexia
o Sensory
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Subjective sensory disturbance, often without evidence of sensory deficit on physical exam or electrodiagnostic tests
Diagnostics
o CSF: high protein, normal cell count (characteristic “albuminocytological dissociation”)
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An elevated cell count instead suggests infection (check for HIV and infections)
o Electrodiagnostic tests may be normal early on
Disease Course
o Peak of symptoms is usually reached within 2-3 weeks
o Usually resolves within 4-6 weeks
Management (patient should be admitted and monitored closely)
o Immunoglobulins (IV) or plasma exchange
o Mechanical ventilation (if necessary)
o NOT steroids
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
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Clinical Features
o Proximal and distal weakness
Diagnostics
o Electrodiagnostic tests show features of acquired demyelination (conduction block, temporal dispersion)
o CSF: high protein
Disease Course
o Lasts > 2 months
Management
o Steroids (prednisone)
o Immunoglobulins (IV)
o Plasma exchange
Parsonage-Turner Syndrome (Brachial Plexus Neuritis or Amyotrophic Neuralgia)
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Etiology
o Diabetes (most common)
o Lupus
o Vasculitis
o Preceding history of viral infection or vaccination (sometimes)
Clinical Features
o Acute onset arm pain with patchy weakness and numbness
o Cannot form circle with tips of the thumb and index finger (anterior interosseous nerve (median) involvement)