Peripheral Neuropathies

Jeffrey T. Reisert, DO

University of New England

Physician Assistant Program
27 AUG 2009

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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 degeneration

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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
Tinnels testing

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Tinnels Testing
Tappingover 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
Bells 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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Bells 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 neuropathy-
Mechanism
Occursdecades after diagnosis
May be ischemic in origin

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Diabetic peripheral neuropathy-
Treatment
Controlof 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)
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
Gehrigs 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
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 20s-30s and men 50s-60s
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
Carpaltunnel (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
Treatmentchemotherapy (Chlorambucil,
cyclophosphamide)
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Charcot-Marie-Tooth disease
An inherited peripheral neuropathy
Usually autosomal dominant
1:2500 population
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
Seenin 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
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
Brachialplexus
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
Harrisons or Cecils 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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