Peripheral Neuropathies
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
27 AUG 2009
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3/18/2016
Contact information
Jeffrey T. Reisert, DO
Tenney Mountain Internal Medicine
251 Mayhew Turnpike
Plymouth, NH 03264-3026
603-536-6355
Jeffrey.T.Reisert@hitchcock.org
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Objectives
Participant will recognize major peripheral
sensory and motor neuropathies including
diabetic neuropathy and Guillain-Barre
syndrome and others
 Student will recognize difference between
mono and polyneuropathies.
 Approach to evaluating patients will be
recalled given a case presentation

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Definitions
Generalized term including disorders of
any cause
 May involve sensory nerves, motor nerves,
or both
 May affect one nerve (mononeuropathy),
several nerves together (polyneuropathy)
or several nerves not contiguous
(Mononeuropathy multiplex)
 May have demyelination or axonal
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
Evaluation
As always, requires history and physical
exam
 Specific attentions to neurological exam
 Typically also requires some electrical
diagnostic study

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History of drug use


Amiodarone
Chemotherapeutics
– Cisplatin
– Taxol

Antibiotics
– Metronidazole
– INH
– Anti-retrovirals

Heavy metals
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Physical exam
Look for thickening of nerves
(Neurofibromas)
 Decreased pinprick, sensation, or
temperature
 Decreased reflexes
 Motor weakness
 Tinnel’s testing

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Tinnel’s Testing
Tapping over nerve creates tingling
 Examples

– Wrist (Carpal tunnel syndrome)
– Elbow (Funny bone)
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Lab evaluation

Might included CBC, Erythrocyte
sedimentation rate, urinalysis, glucose,
serum protein electrophoresis, thyroid
function testing
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Electrical diagnosis

Demyelination
– Slows nerve conduction velocity
– Conduction block possible

Axonal degeneration
– Decreases amplitude of action potentials
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Electrical diagnosis

Helps differentiate between:
– Muscle vs. nerve problem vs. neuromuscular
junction
– Root vs. distal nerve location
– Single vs. multiple nerves
– Upper vs. lower motor neuron dz
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Nerve biopsy

May be required to rule out:
–
–
–
–
Vasculitis
Amyloid
Leprosy
Sarcoidosis
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Mononeuropathies
Ulnar neuropathy
 Carpal tunnel syndrome
 Tarsal tunnel syndrome
 Bell’s palsy

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Carpal tunnel syndrome
Perhaps the most common
mononeuropathy
 Entrapment of median nerve in the wrist
 Results in paresthesias of thumb, index,
and middle finger; Weakness of the
abductor pollicus brevis
 Tingling fingers, weak thumb, loss of
“meat” of the APB muscle (atrophy)

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Carpal tunnel syndrome-Causes

Usually due to overuse
– Typing probably okay (argued)

Other causes
– Arthritis


–
–
–
–
Osteoarthritis
Rheumatoid arthritis
Infiltrative diseases
Hypothyroidism
Diabetes
Pregnancy
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Carpal tunnel syndrome-Treatment


Treatment is usually surgical resection of carpal
ligament
Other treatments may help, too
– Stretches
– Splints


Cock-up wrist splints
Night time use only ?
– Anti-inflammatory medications


Oral (non-steroidal)
Injections
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Ulnar neuropathy
Just distal to the elbow cubital tunnel
entrapped
 Results in a claw hand if severe

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Tarsal tunnel syndrome
Distal tibial nerve entrapment distal to the
medial malleolus
 Etiology: Trauma, poor shoes, cyst or
ganglion, and arthritis
 Symptoms include numbness on bottom of
feet, pain in ankle, and weak toe flexors
 Treatment is typically surgical

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Bell’s palsy



Inflammation of 7th cranial nerve
One sided facial paralysis
Mechanism not understood
– Virus implicated
– Lyme disease?

Treatment
–
–
–
–
May need to tape eye, especially at night
Herpes treatment/Antivirals
Prednisone?
Usually resolves with time
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Herpes Zoster
Reactivation of chicken pox virus
 Lancenating pain followed in 3-4 days by
blistering rash
 Post herpetic neuralgia in 5% of those
affected (next slide)

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Post Herpetic Neuralgia


Risk increases with age.
Treatment
– Carbamazepine (Tegretol®)
– Tricyclic anti-depressants


Amitriptyline (Elavil®)
Others
– Newer agents (anti-epileptics)


Gabapentin (Neurontin®)
Pregabalin (Lyrica®)
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Polyneuropathies


Can be due to a toxic or metabolic state
Many symptoms possible
– Tingling/Prickling/Stabbing/Burning
– Later dysesthesias (Abnormal sensation where light
touch causes pain)
– Sensory or motor loss with possible decreased
reflexes
– Weakness, gait disturbance
– Flexor contractures

Stocking-glove distribution (defects worse
distally)
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Diabetes
Symmetrical or asymmetrical
 Distal sensory typical (feet!)
 Autonomic loss

– Vasomotor disturbance
– Abnormal sweating
– Impotence

Pain
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Diabetic peripheral neuropathyMechanism
Occurs decades after diagnosis
 May be ischemic in origin

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Diabetic peripheral neuropathyTreatment
Control of glucose perhaps most important
 Medicines may help, though

–
–
–
–
Tricyclic anti-depressants
Gabapentin (Neurontin®)
Pregabalin (Lyrica®)-Next slide
Duloxetine (Cymbalta®)-Next slide
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Pregabalin (Lyrica®)




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
Newer, more expensive agent
Mechanism not entirely understood
Binds to alpha2-delta site in central nervous
system
Antinociceptive
Antiseizure
Uses:
– Painful DM peripheral neuropathic pain
– Post herpectic neuralgia
– Partial onset seizures
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Duloxetine (Cymbalta®)

Serotonin and norepinephrine reuptake
inhibitor
– Inhibits pain via descending pain pathways
– Antidepressant and pain effector
– Use in depression and diabetic neuropathic
pain
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HIV
Most commonly is a distal sensory
polyneuropathy
 Must distinguish from toxicity of
nucleoside analogues used to treat disease
 Zidovudine may help reduce

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Lyme disease
Inflammatory disease of spirochete
(bacteria) Borrelia from bite of Ixodes tick
 Occurs weeks to months after onset of
disease (Early disseminated disease, or late
disease)
 Sensory or painful neuropathy
 Variable/patchy disease

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Leprosy
Mycobacterial disease
 Hypoesthesia
 Anesthesia

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Pure motor neuropathies
Amyotrophic lateral sclerosis (ALS, Lou
Gehrig’s disease)-Lower motor neuron
disease. Death within 5 years.
 Poliomyelitis-Spinal cord disease
 Spinal muscular atrophies
 Guillain-Barre syndrome-A peripheral
nerve disorder
 Myasthenia gravis

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Guillain-Barre syndrome (GBS)
Acute (hours to days) fulminant
polyradiculoneuropathy
 Autoimmune inflammatory demyelination

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GBS-Symptoms
Motor paralysis with or without sensory
symptoms (pain) however sensation is
preserved
 Areflexia
 Legs>Arms
 May have trouble swallowing, or with
airway requiring ventilation

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GBS-Etiology
Often preceded by URI or GI infection
 Campylobacter jejuni implicated most in
North America
 CMV, EBV, and immunization also
implicated

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GBS-Diagnosis
Increased CSF protein without increase in
cells (absence of pleocytosis)
 Electrical diagnosis shows slow
conduction velocity

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GBS-Treatment
High dose IV gamma globulin (IVIG).
2g/kg five consecutive days
 Plasmapheresis

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GBS-Prognosis
85% fully recover
 <5% mortality
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Myasthenia Gravis


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Disorder of neuromuscular junction
Antibody attack of acetylcholine receptors
As a result, less post synaptic receptors
Weakness and fatigability of muscles
Eye lids and cranial nerves with diplopia and
ptosis
1 in 7500 people
– Peak in women 20’s-30’s and men 50’s-60’s

Cure unknown, but treatable
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Myasthenia gravis-Diagnosis and
Treatment
Anticholinesterase drug such as
edrophonium (Tensilon®) or
pyridostigmine (Mestinon®)
 Thymectomy
 Immunosupression (steroids,
azathioprine/cyclosporin (chemo drugs)
 Immunoglobulin)

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Motor & Sensory Neuropathies
Carpal tunnel (covered earlier)
 Chronic inflammatory demyelinating
polyneuropathy (CIDP)
 Monoclonal gammopathy
 Charcot-Marie-Tooth

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Chronic inflammatory
demyelinating polyneuropathy
(CIDP)
Gradual onset
 Motor and sensory symptoms
 75% recovery/Death rare
 Other than slow onset, similar to GBS
 Treatment same (IVIG 0.4g/kg x5days)

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Neuropathies with monoclonal
gammopathy

Multiple myeloma
– Plasma cell disease producing lytic bone lesions
– Sensory and motor disease due to demyelination

Monoclonal gammopathy of unknown
significance (MGUS)
– Similar to CIDP
– Para protein affects myelin sheath

Treatment chemotherapy (Chlorambucil,
cyclophosphamide)
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Charcot-Marie-Tooth disease

An inherited peripheral neuropathy
– Usually autosomal dominant
– 1:2500 population


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Distal muscle weakness, impaired sensation, and
decreased reflexes
Foot deformities from atrophy
Seen earlier in life (first 2-3 decades)
Treat foot deformities
There are also other less common inherited
peripheral neuropathies
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Other pure sensory neuropathies

Drug induced
– Cisplatin
– Taxol

Paraneoplastic syndromes
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Paraneoplastic peripheral
neuropathies
Seen in cancers and lymphomas
 Axonal degeneration (myasthenia-like)

– Guillain-Barre
– Monoclonal gammopathies
– Eaton-Lambert myasthenic syndrome
Weakness of proximal muscles of lower
extremities
 Ptosis and diplopia
 Treat like MG, plus treat the tumor

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Autonomic neuropathy
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AKA dysautonomia
Loss of function
Postural hypotension (May lead to syncope)
No sweating
Feel cold
Bladder or bowel problems
Dry mouth
Impotence
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Plexopathies
Brachial plexus
 Lumbosacral plexus
 Due to neuritis, trauma, tumor, or radiation
 Motor and sensory

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Mononeuritis Multiplex
Loss of non-contiguous nerves
 May be simultaneous or sequential
 Etiology: Toxins, chemicals, solvents,
alcohol, medical conditions

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Summary
There are many types of peripheral
neuropathy
 Broadly, they can be divided by onset of
symptoms, location, and by sensory or
motor involvement

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Where to Get More Information
Harrison’s or Cecil’s textbook of Internal
Medicine
 Natural History of Peripheral Neuropathies
in patients with NIDDM. NEJM Jul 13
1995.

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Questions?
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