1

Pathophysiology of nerve damage and polyneuropathy

Polyneuropathy affects the peripheral nerve and is the umbrella terms for a family of
symptoms. Depending on the triggering disease the motor, sensory or autonomic fibers are
altered to a varying degree which gives a variable symptomology to the clinical picture. The
triggering disease may be inherited due to genetic abnormalities but is more often due to a
great variety of different acquired etiologies. In the majorities of cases the symptoms have a
gradual onset and are therefore not immediately recognized by the individual. The perception
of the situation changes, when already major morphological damage have occurred on the
peripheral nerve and the patient starts to suffer from numbness, tingling, burning, gait problems
or loss of muscle force or pain. To prevent these damages and keep the quality of life of the
patient early diagnose is a major and important challenge.

Structural-anatomical injuries allow a classification due to lesions of the myelin sheath, the
axon, the neuron or damage due to vascular ischemic events. Electrophysiology can help to
differentiate between these states as this is important for prognosis. It is known that a
myelinopathy leaves the axon intact and remyelination can reestablish nerve function. This
happens in a shorter time as in an axon lesion. The axonopathies cause the nerve to die in a
distal to proximal fashion (Dying back-neuropathy). As axonal outgrowth is usually slower then
remyelination, therefore, return of function takes longer. The time frame of restoration and the
possibility to reverse the damaged and disturbed neurons function relies heavily on the severity
and influence time of the causing agent.

According to the symptoms distribution, the most common clinical picture is a distal, symmetric
sensorimotor polyneuropathy, but sometimes it manifests as a mononeuropathy or multifocal
neuropathy. The symmetric forms can be classified as predominantly having motor or sensory
disturbances or a mixture of sensorimotor manifestations. A predominance of autonomic
features can occur in diabetes, amyloidosis, and after isoniazid, arsenic and alcohol exposure.

A polyneuropathy is most commonly induced by metabolic disorders; so at least 25% of

diabetics are affected with a gradual onset of sensorimotor or autonomic nerve failure.
Amongst them 20 % develop neuropathic pain. The mono- and multiple mononeuropathies
have in diabetics an acute onset. Most peripheral nerves can be affected, common is among
cranial nerves oculomotor paresis. Other metabolic disorders are hypothyroidism, renal failure
or vitamin deficiency due to malnutrition, malabsorption in gastrointestinal disorders, or other
reasons.

A polyneuropathy can also be triggered by life style habits like increased alcohol intake. In
alcoholic neuropathy the axon is predominantly affected. At first it starts with pain, paresthesia
and paresis in the legs and later symptoms occur in the arms, all problems manifest in a distal
to proximal progression. Autonomic involvement, here and in all other disease states, induces
sweating of soles and palmar surface, thinning of the skin and impotence.

But there are many more illnesses that trigger nerve damage like autoimmunological and
infection diseases, malignancies or treatment side effects arising from treating these
sicknesses. To find the reason for a polyneuropathy is often not easy. In up to 30 to 40% of
1
 2

cases the etiology may remains unknown. Specialized centers can yield a higher percentage
of positive results.

Polyneuropathy treatment depends in the first place on finding the triggering etiology. Treating
this underlying disorder is the paramount goal. But treatment is not always successful. Due to
the noxious events, the peripheral nerve and its motor, sensory and autonomic fibers undergo
over time a steadily progressing damage and regeneration. There is at first a very good
regenerative capacity of neuron, axon and myelin. But the amount of restitution depends on
severity and time course of the damage.
Constant damage and restoration limits over time the nerves potential to regenerate. The
chance to restore nerve-function will usually end, when more then 50 % of the originally present
nerve fibers are lost. Therefore, this clinical proven point of no return demands an early
diagnosis of polyneuropathies. This is possible with an awareness and knowledge for this
disease by the physicians and education of the population, especially the patient population
who is under danger to suffer from polyneuropathy.

Take home message: Prevention is far more effective then treatment.

Peripheral nerve (motor neuron)

Normal Nerve tissue, normal fiber density Axonal Neuropathy, loss of fibers, point of no return

Reference: Nix W. Muscle, nerves and pain; Berlin, Heidelberg: Springer-Verlag; 2017.