An Approach to Peripheral Neuropathy

Peter-Brian Andersson MBChB,BSc(Med)(Hons),DPhil

http://www.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/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…

www.ama-assn.org/ ama/pub/category/7172.html

• Mononeuropathy?

• Polyneuropathy? multiple nerves

contiguous typically length dependent

(“stocking-glove”)

Polyneuropathy is common! 2.4% (8% over 55 yr)

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://www.neuro.wustl.edu/neuromuscular/pathol/nervenl.htmhttp://fulton.edzone.net/cites/winkler-science/team1/chap8.html

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

Loss of function

“- symptoms”

Disturbed function

“+ symptoms”

Motor nerves Wasting

Hypotonia

Weakness

Hyporeflexia

Orthopedic deformity

Fasiculations

Cramps

The clinical response to motor nerve injury

www.neuro.wustl.edu/neuromuscular/pics/people/patients/Hands/handatrophymnd3.jpg

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 sensory nerve injury

Loss of function

“- symptoms”

Disturbed function

“+ symptoms”

Autonomic nerves ↓ Sweating

Hypotension

Urinary retention

Impotence

Vascular color changes

↑ Sweating Hypertension

The clinical response to autonomic nerve injury

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.

Copyright ©2002 BMJ Publishing Group Ltd.

Hughes, R. A C BMJ 2002;324:466-469

Using nerve conduction studies in polyneuropathy

http://www.neuroanatomy.wisc.edu/SClinic/Weakness/Weakness.htm

= Slow!

= Low!

= Slow!

http://missinglink.ucsf.edu/lm/ids_104_musclenerve_path/student_musclenerve/nervepath.html

Normal Nerve Axonal degeneration

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

http://www.neuro.wustl.edu/neuromuscular/pathol

Normal

Demyelination

Normal

Demyelination

Myelinopathies

• Unusual by comparison with axonopathies• Clues: hypertrophic nerves on exam

global arreflexiaweakness without wastingmotor >> sensory deficitsNCS can discriminate inherited

from acquired

• NCS: Distal motor latency prolonged (>125% ULN)Conduction velocities slowed (<80% LLN)May have conduction block

EMG: 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: e.g. Charcot-Marie-Tooth disease (HMSN)Infectious: e.g. LeprosyInflammatory: e.g. Guillain Barre syndrome (AIDP)Neoplastic: e.g. Monoclonal gammopathyMetabolic: e.g. DiabetesDrug: e.g. VincristineToxic: e.g. Ethanol

How then are we to sort through the causes to make an etiologic diagnosis?...

Use the 6 D’s….

1. What is the distribution of the deficits?2. What is the duration?3. What are the deficits (which fibers are involved)?4. What is the disease pathology (axonal or

demyelinating or mixed)5. Is there an inherited (developmental) neuropathy? 6. 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?

• Most polyneuropathies are chronic – ++months-yrs

• Acute polyneuropathies e.g. Guillain Barre syndrome Vasculitis

• Relapses and remissions e.g. Intermittent toxin exposure

Ask: Acute or Chronic?

3. What are the deficits (which fibers affected)?

• If predominant motor fibers think of:Guillain Barre syndromeLead toxicityCharcot-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:DiabetesAmyloidDrugs 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?

e.g.

Cancer drugs like vincristine and paclitaxel

Antibiotics like chloroquine, ethambutol, isoniazid and metronidazole

Cardiac medications like amiodarone

e.g. Glue sniffingArsenic

Demyelinating Axonal

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

^

^Motor

UMN

LMN

Sensory

>

^

v

v

v

<

^

^<Autonomic

PSy

Sy

^

cord

m.drg

v

Spth

DorC

v

T1-L2

III,VII,IX,X S2-4

th

c.

r.g.n.

The Motor Unit

From Dumitru, D. Electrodiagnostic Medicine, Hanley & Belfus. Philadelphia. 1995