An Approach
to Peripheral
Neuropathy
Peter-Brian Andersson
MBChB,BSc(Med)(Hons),DPhil
http://www.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20
Reviews/Exam%204%20Review/CH%2013%20Peripheral%20Nerve%20Histology.htm
The 3 questions of clinical neurology…
#1. Where is the lesion?
#2. What is the etiology?
#3. What is the treatment?
www.ama-assn.org/ ama/pub/category/7172.html
The patterns of peripheral
neuropathy…
• Mononeuropathy?
• Polyneuropathy?
multiple nerves
contiguous
typically length dependent
(“stocking-glove”)
Polyneuropathy is common! 2.4%
(8% over 55 yr)
www.ama-assn.org/ ama/pub/category/7172.html
Overview of the Lecture –Mastering polyneuropathy
#1. Where is the injury?
The syndrome depends on:
• what modalities are injured,
• what fibers are injured,
• whether axon or myelin (or both) injured.
#2. What is the etiology?
Tricky – hence an approach necessary at the bedside.
#3. What is the treatment?
Depends on reversing the underlying cause.
Three common examples
http://fulton.edzone.net/cites/winkler-science/team1/chap8.html
http://www.neuro.wustl.edu/neuromuscular/pathol/nervenl.htm
The clinical effect of a polyneuropathy depends on
1) what modalities involved
2) what fibers are effected
3) whether the injury is axonal or demyelinating.
Adapted from http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm
The clinical response to motor nerve injury
Loss of function
“- symptoms”
Motor nerves
Wasting
Hypotonia
Weakness
Hyporeflexia
Orthopedic deformity
Disturbed function
“+ symptoms”
Fasiculations
Cramps
www.neuro.wustl.edu/neuromuscular/pics/people/patients/Hands/handatrophymnd3.jpg
The clinical response to sensory nerve injury
Loss of function
“- symptoms”
Disordered function
“+ symptoms”
Sensory
“Large Fiber”
↓ Vibration
↓ Proprioception
Hyporeflexia
Sensory ataxia
Paresthesias
Sensory
“Small Fiber”
↓ Pain
↓ Temperature
Dysesthesias
Allodynia
The clinical response to autonomic nerve injury
Loss of function
“- symptoms”
Disturbed function
“+ symptoms”
Autonomic nerves ↓ Sweating
↑ Sweating
Hypertension
Hypotension
Urinary retention
Impotence
Vascular color changes
http://www.neuro.wustl.edu/neuromuscular/nother/skel.html#nosteo
The two types of peripheral neuropathies:
axonopathies and myelinopathies
From Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed.
Using nerve conduction studies in polyneuropathy
= Low!
= Slow!
= Slow!
Copyright ©2002 BMJ Publishing Group Ltd.
Hughes, R. A C BMJ 2002;324:466-469
http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm
Normal Nerve
Axonal degeneration
http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html
Wallerian Degeneration
http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html
Axonopathies
• By far the majority of the toxic, metabolic and endocrine
causes
• NCVs: CMAPs ↓ 80% lower limit of normal w/o or min
velocity or distal motor latency change.
• Legs>> arms.
• EMG: Signs of denervation (acute, chronic) and
reinnervation
Segmental Demyelination
Normal
Demyelination
Normal
Demyelination
http://www.neuro.wustl.edu/neuromuscular/pathol
Myelinopathies
• Unusual by comparison with axonopathies
• Clues:
hypertrophic nerves on exam
global arreflexia
weakness without wasting
motor >> sensory deficits
NCS can discriminate inherited from acquired
• NCS:
EMG:
Distal motor latency prolonged (>125% ULN)
Conduction velocities slowed (<80% LLN)
May have conduction block
Reduced recruitment w/o much denervation
Question #2. What is the etiology?
Only a limited number of ways a peripheral
nerve can react to injury, thus a multitude of
different etiologies can cause similar effects…
Problem: The multitude causes of peripheral neuropathy!!!
Inherited:
Infectious:
Inflammatory:
Neoplastic:
Metabolic:
Drug:
Toxic:
e.g. Charcot-Marie-Tooth disease (HMSN)
e.g. Leprosy
e.g. Guillain Barre syndrome (AIDP)
e.g. Monoclonal gammopathy
e.g. Diabetes
e.g. Vincristine
e.g. Ethanol
How then are we to sort through the causes to
make an etiologic diagnosis?...
Use the 6 D’s….
1.
2.
3.
4.
5.
6.
What is the distribution of the deficits?
What is the duration?
What are the deficits (which fibers are involved)?
What is the disease pathology (axonal or
demyelinating or mixed)
Is there an inherited (developmental) neuropathy?
Is there drug/toxin exposure?
1. What is the distribution of the deficits?
• Asymmetry
1. Mononeuropathy
2. Mononeuritis multiplex – e.g. vasculitis
• Symmetric (glove/stocking) = polyneuropathy
2. What is the duration?
Ask: Acute or Chronic?
• Most polyneuropathies are chronic – ++months-yrs
• Acute polyneuropathies
e.g. Guillain Barre syndrome
Vasculitis
• Relapses and remissions
e.g. Intermittent toxin exposure
3. What are the deficits (which fibers affected)?
• If predominant motor fibers think of:
Guillain Barre syndrome
Lead toxicity
Charcot-Marie-Tooth disease
• If pure sensory/ severe proprioceptive deficit, think of sensory
neuronopathy:
Carcinoma (paraneoplastic)
Vitamin B6 toxicity
• If autonomic nerves involved (small fiber) think of:
Diabetes
Amyloid
Drugs like vincristine, ddI, ddC
4. What is the disease pathology?
• The vast majority are axonal.
• Demyelination a key finding because its causes are
relatively few.
• If demyelination uniform the cause is hereditary.
e.g. Charcot-Marie Tooth type I (HMSN)
• If otherwise unremarkable chronic sensorimotor
axonal polyneuropathy… exclude
alchohol, diabetes, hypothyroidism, uremia,
B12 deficiency & monoclonal gammopathy
5. Is there an inherited (developmental) neuropathy?
• Among the most common!
• Clues
– orthopedic deformities (feet, spine)
– long duration
– indolent progression
– few “positive” symptoms
– examine/question the family members!
6. Drug or toxin exposure?
Demyelinating
e.g.
Glue sniffing
Arsenic
Axonal
e.g.
Cancer drugs like vincristine
and paclitaxel
Antibiotics like chloroquine,
ethambutol, isoniazid and
metronidazole
Cardiac medications like
amiodarone
Polyneuropathy Example #1
•
•
•
•
•
58 year old movie industry executive
2 yrs toe numbness, paresthesias and pain
Stocking numbness of toes with absent ankle jerks
No medical history or family history or medications
Multiple consultations & lab testing without etiologic
diagnosis
(A common axonal polyneuropathy)
Ethanol Neuropathy
•
•
•
•
•
•
•
•
Among the most common neuropathies worldwide
Chronic
Numbness, paresthesias, pain in stocking distribution
Sensory >>> Motor
Loss of ankle reflexes
History!
Ethanol toxicity and nutritional deficiency
Vitamin B1 (thiamine)
Polyneuropathy Example #2
• 23 yr old professional baseball player with no past
medical or family history & no medications.
• Severe pain in back and flank followed by
weakness over hours to inability to walk.
• Severe weakness legs, milder weakness arms
• Arreflexia
• Numbness of feet
• Diarrheal illness 2 weeks ago
(A common demyelinating polyneuropathy)
Guillain-Barre Syndrome
•
•
•
•
•
•
Rapid, severe, typically ascending paralysis
Post infectious in 60%
Paresthesias, pain, numbness
Autonomic nerves
Reflexes lost
Cytoalbuminologic dissociation in the CSF
Polyneuropathy Example #3
•
•
•
•
•
•
55 year old obese woman
Family history positive for diabetes
4-5 years of nocturia and 1-2 years of polyuria
Dry skin over the feet
Stocking numbness in all modalities to the ankles
Absent ankle reflexes
(A common mixed axonal & demyelinating polyneuropathy)
Diabetic Polyneuropathy
•
•
•
•
•
•
Multiple forms of neuropathy in diabetes
Sensory >>> motor polyneuropathy
Autonomic involvement common
CSF protein frequently elevated
Glucose control!
Foot care
Peripheral Neuropathy in summary…
1. Patterns: mononeuropathy, mononeuropathy multiplex or
polyneuropathy – focal, multifocal or diffuse
2. “Signature” manifestations of a polyneuropathy depend
on what modalities affected (motor, sensory, autonomic)
and whether it is axonal or demyelinating.
3. Examination, NCS/EMG & biopsy can discriminate
axonopathy from myelinopathy
4. The multiple potential etiologies of polyneuropathy are
manageable recognizing patterns of disease by the 6 Ds
Plan of the Nervous System
UMN
c.
vv
t
h
m.
^
LMN
^
Motor
vv
v
c
o
r
d
drg
T1-L2
^
DorC
>
<
Sy
^
Spth
III,VII,IX,X
S2-4
r.
g.
n.
PSy
Sensory
Autonomic
^
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The Motor Unit
From Dumitru, D. Electrodiagnostic Medicine, Hanley & Belfus. Philadelphia. 1995