PERIPHERAL NEUROPATHY

PHYSIOLOGY
Pain and temperature sensation :
unmyelinated and small myelinated Ad
fibers,
Vibratory sense, proprioception, and the
afferent limb of the tendon reflex : large
myelinated Aa and Ab fibers.
Light touch : both large and small
myelinated fibers.
 FIVE QUESTION APPROACH

1. Fiber type
2. Pattern of distribution

5. Pathology

3. Temporal course

4. Key features
 1.What is the fiber type involved?
(motor, large sensory, small sensory, autonomic,
combination)
2. What is the pattern of distribution?
(distal or proximal, symmetric or asymmetric)
3. What is the temporal course?
(acute, chronic, progressive, stepwise, relapsing
remitting)
4. Are there any key features pointing to a specific
etiology? (toxic/nutritional/malignancy)
5. What is the pathology?
(axonal, demyelinating)
 Pathological Process
(1) Wallerian degeneration, which is the
response to axonal interruption;
(2) Axonal degeneration or axonopathy;
(3) Primary neuronal degeneration or
neuronopathy;
(4) Segmental demyelination
 Wallerian degeneration
Any type of mechanical injury that
causes interruption of axons leads to
wallerian degeneration (degeneration of
axons and their myelin sheaths) distal to
the site of transection.
 Axonal degeneration
Most common pathological reaction of
peripheral nerve
Caused by :Systemic metabolic disorders,
toxin exposure, and some inherited
neuropathies
Also called dying-back or length-dependent
neuropathy:
The myelin sheath breaks down along with the
axon in a process that starts at the most distal
part of the nerve fiber and progresses toward
the nerve cell body.
 Dying-back neuropathy
Clinically, presents with symmetrical, distal
loss of sensory and motor function in the lower
extremities that extends proximally in a graded
manner.
The result is sensory loss in a stocking-like
pattern, distal muscle weakness and atrophy,
and loss of ankle reflexes
 Neuronopathy
Primary loss or destruction of nerve cell bodies with
resultant degeneration of their entire peripheral and
central axons.
Either lower motor neurons or dorsal root ganglion cells
may be affected.
When anterior horn cells - poliomyelitis or motor neuron
disease: focal weakness without sensory loss
Sensory neuronopathy, or polyganglionopathy :damage
to dorsal root ganglion neurons - inability to localize the
limb in space, diffuse areflexia, and sensory ataxia.
 Segmental demyelination
The term implies injury of either myelin sheaths
or Schwann cells, resulting in breakdown of
myelin with sparing of axons
This occurs in immune-mediated demyelinating
neuropathies and in hereditary disorders of
Schwann cell/myelin metabolism.
 Demyelinating neuropathies

Relative sparing of temperature and pinprick

sensation +
1.Early generalized loss of reflexes,
2.disproportionately mild muscle atrophy
3.presence of proximal and distal weakness,
4.neuropathic tremor
5. palpably enlarged nerves
 Diagnostic Clues from the History
1.motor 2.sensory 3.autonomic disturbances.
Seek both positive and negative symptoms.
A. Motor:
Positive :
Muscle cramps, fasciculations, myokymia, or
tremor
Negative :
early distal toe and ankle extensor weakness,
resulting in tripping on rugs or uneven ground
 Sensory symptoms
Positive :
prickling, searing, burning, and tight bandlike
sensations.
Paresthesia: Unpleasant sensations arising
spontaneously without apparent stimulus
Allodynia: perception of nonpainful stimuli as
painful.
Hyperalgesia: Painful hypersensitivity to noxious
stimuli
Neuropathic pain: cardinal feature of many
neuropathies.
 Autonomic dysfunction
Orthostatic lightheadedness,
Fainting spells,
Sweating reduced or excessive,
Heat intolerance,
Bladder, Bowel, and Sexual dysfunction.
Anorexia, early satiety, nausea, and vomiting
 TEMPORAL CLUES
Onset, duration, and evolution of symptoms
Tempo of disease : acute, subacute, or chronic
Course: monophasic, progressive, or relapsing
Acute presentations: Guillain-Barr syndrome
(GBS), acute porphyria, vasculitis, toxic
neuropathies.
Relapsing course : (CIDP), acute porphyria,
Refsum's disease, hereditary neuropathy with
liability to pressure palsies (HNPP), familial
brachial plexus neuropathy, and repeated
episodes of toxin exposure.
 Constitutional symptoms
Weight loss, malaise, and anorexia.

DM [HIV]
hypothyroidism drug use
chronic renal failure Vitamin B6 toxicity
liver disease alcohol and dietary habits
intestinal malabsorption exposure to solvents,
malignancy pesticides, or heavy
connective tissue diseases metals.
 Mononeuropathy

Focal involvement of a single nerve and

implies a local process:
Direct trauma
compression or entrapment
vascular lesions
neoplastic compression or infiltration
 Mononeuropathy multiplex
simultaneous /sequential damage to multiple
noncontiguous nerves.
Ischemia caused by vasculitis
Microangiopathy in diabetes mellitus
Less common causes : Infectious,
granulomatous, leukemic, or neoplastic
infiltration, Hansen's disease (leprosy) and
sarcoidosis.
 Polyneuropathy
Characterized by symmetrical, distal motor and
sensory deficits that have a graded increase in
severity distally and by distal attenuation of
reflexes,
Rarely predominantly proximal:(E.g: acute
intermittent porphyria).
The sensory deficits generally follow a length-
dependent stocking-glove pattern
 Motor deficits
Dominate the clinical picture in
1. AIDP/CIDP

2. Hereditary motor and sensory neuropathies,

3. Neuropathies associated with osteosclerotic

myeloma, porphyria, lead and organophosphate
intoxications, and hypoglycemia.
 Pattern of weakness
Asymmetrical motor weakness without
sensory loss suggests motor neuron disease or
multifocal motor neuropathy with conduction
block
Neuropathies with Facial Nerve Involvement

Guillain-Barr syndrome

Chronic inflammatory polyradiculoneuropathy

Lyme disease

Sarcoidosis

HIV
 Predominant Sensory

Diabetes Celiac disease

Carcinoma; Toxicity with cisplatin,
thalidomide, or
Sjgren's syndrome;
pyridoxine
Dysproteinemia;
Inherited and idiopathic
AIDS sensory neuropathies
vitamin B12 deficiency
 Autonomic dysfunction
GBS

Diabetes

Amyloid sensorimotor polyneuropathy

 Small-Fiber Neuropathies

Idiopathic small fiber neuropathy

Diabetes mellitus
Amyloid neuropathy
HIV-associated distal sensory neuropathy
Hereditary sensory and autonomic neuropathies
 Large-fiber
Areflexia

Pseudoathetosis

Loss of joint position and vibration sense

Positive Romberg's sign

 Electrodiagnostic studies
(1) Confirming the presence of neuropathy,

(2) Locating focal nerve lesions,

(3) Nature of the underlying nerve pathology

 Distal motor latency prolonged

Nerve conduction velocity slow

Reduced action potential

 Nerve biopsy
In vasculitis, amyloid neuropathy, leprosy, CIDP,
Inherited disorders of myelin, and rare
axonopathies

The Sural nerve is selected most commonly

The superficial peroneal nerve alternative;
:advantage of allowing simultaneous biopsy of the
peroneus brevis muscle through the same incision.
This combined nerve and muscle biopsy
procedure increases the yield of identifying
suspected vasculitis
 Neuropathies + Serum Autoantibodies

Antibodies against Gangliosides

GM1 : Multifocal motor neuropathy
GM1, GD1a : Guillain-Barr syndrome
GQ1b : Miller Fisher variant

Antibodies against Glycoproteins

Myelin-associated glycoprotein : MGUS

Antibodies against RNA-binding proteins

Anti-Hu, antineuronal nuclear antibody 1: Malignant
inflammatory polyganglionopathy
 SUMMARY
A. Clinical pattern of neurologic findings
Polyneuropathy, Neuronopathy,
Mononeuropathy, Multiple mononeuropathy,
Plexopathies
B. Functional disturbance: Motor, Sensory,
Autonomic, Mixed
C. Mode of onset :
1.Acute 2.Subacute 3.Chronic
4.Relapsing

 D. Pathological and electrophysiological

criteria:
1.Demyelinating disease vs Axonopathy
2.Wallerian degeneration - trauma
3.Dying back neuropathy - toxic, metabolic

E. Etiology:
Metabolic, immune mediated, toxic, vasculitis,
dysproteinemic, inherited, Nutritional
deficiency

 F. Diagnosis
1.Clinical data
2.Electrophysiologic test : NCS, EMG
3.Biochemical test : metabolic, nutritional,
toxic
4.CSF study
5. Nerve & muscle biopsy
6. Measurement of Ig & anti-neural antibody
7. Genetic study