notes by dr Claudio Italiano
Diabetic neuropathy is an alteration of the peripheral nervous system, both symptomatic and asymptomatic, arising in the course of diabetes mellitus and caused by it. It can affect both the somatic component and the autonomy of the peripheral nervous system.
- the symmetrical distal polyneuropathy of the sensory-motor and / or autonomic type
- proximal motor neuropathy
- focal neuropathies that resolve spontaneously,
- entrapment neuropathies
- autonomy neuropathy
- the mixed forms
Numerous epidemiological studies have shown that symmetrical distal polyneuropathy is present in 30-40% of diabetic patients, while only 10% are symptomatic.
The different clinical forms recognize different etiopathogenesis moments; it
goes from the ischemic fact of the nerve which is the predominant cause of the
focal forms, while the compressive mechanical factor plays a major role in the
entrapment ones.
In the pathogenesis of symmetric distal polyneuropathy and autonomic neuropathy,
it is thought that the endoneural ischemia resulting from mciroangiopathy is the
triggering factor. The factors of non-enzymatic glycation and auto-oxidation and
the activation of the path of the polyols which induce oxidative stress,
together with the pathology of the small vessels (microangiopathy), at the basis
of trophism and of the change in the nerve fiber, are also involved. Under some
conditions it results in a decrease in nerve growth factor or NGF ("Nerve Growth
factor").
The nerve is formed by an ectodermal part and a connective part:
The ectodermal part is formed by the axons of the medullary motor neurons and
the encephalic trunk, and of the neurons of the sensory and sympathetic ganglia
and of the Schwann cells; the axoplasm is free of ribosomes, but rich in
mitochondria and vesicles of smooth ER, of neurofibrils formed by actin and
microtubules of tubulin, part of the cytoskeleton, which by ATP splitting deals
with axonal movements (slow flow of 10 mm per day for enzyme transport + rapid
flow of 400 mm per day for vesicles and organelles + retrograde flow for
recycling of neurotransmitters and proteins, with a negative feedback function
on protein synthesis); Myelinated fibers are 1/5 of total, with a diameter
greater than 2 microns, formed by wrapping of Schwann cell with interruption by
Ranvier node that allows conduction of the jump impulse; the amyelinated cells
are in groups in a single Schwann cell, and form postganglionic branches of
sympathetic and tactile sensitivity, thermal, non-discriminatory painful, have
conduction velocities of 0.5 - 2 m / s.
Connective tissue forms three layers: internal "endonervio" of connective lasso
with collagen fibers, fibroblasts and mast cells, covers every single nerve
fiber + perinervium of flat connective cells mixed with collagen and elastic
fibers, covers more nerve fibers to form fasciculi, and barrier form regulation
of the passage of substances + external "epinervium", of collagen, elastic
fibers, fat cells and fibroblasts, wraps the entire nerve and the vasa nervorum,
in continuity with the medullary dura mater and of the encephalic trunkAnatomia patologica
There are several types of degeneration affecting the nerve fiber:
- Wallerian degeneration following interruption of the axon or nerve (axonotmesis)
with maintenance of connective tissue: after 48 hours the axon swells with
myelinated destruction and phagocytosis of globular lipid formations, after a
few days there are buds regeneration with recovery of 1 mm per day.
- Axonal degeneration following metabolic alteration: initially affects the
distal parts of the fiber with slow proximal progression, dying-back. or
retrograde death that depends on the quality of metabolic control and metabolic
insults. However, if the pathogenic noxa disappears, the nerve may have
functional recovery; if the myelin sheath suffers, as for diabetes, the nerve
remains in pain.
- Segmental demyelination for primitive damage to Schwann cells due to metabolic
alteration, inflammatory process, toxic damage: there is a progressive slowing
of the impulse, up to the block when demyelination affects a stretch of fiber
greater than 3 internodes, there is axonal suffering and attempt of
remielination by new proliferating cells, but the succession of demyelination
and reemilinization processes causes a thickening of the fiber by interposition
of fibroblasts and collagen, with formation of palpable onion bulb fibers on the
skin (hypertrophic polyneuropathies of Dejerine-Sottas, amyloidosis and chronic
inflammatory demyelinating agents).
Diabetic neuropathy is characterized by paresthesia, dysaesthesia, pain located
at the distal points of the limbs with "sock" and "glove" distribution.
Sometimes, in the most severe cases, motor deficits appear. Clinical
manifestations are symptomatic orthostatic hypotension, gastroparesis, nocturnal
watery diarrhea, gustatory sweating, sexual impotence.
Classification
There are 100 types of polyneuropathies and different ways of classifying them.
In the pathological anatomic sense they can be classified as axonal if they hit
axon, or demyelinating if they hit Schwann cells. But better classification is
etiological: inflammatory demyelinating and autoimmune (Guillain-Barrè) + from
infectious agents (HIV, Epstein-Barr, leprosy, sarcoidosis) + metabolic (diabetic,
porphyria, hypothyroidism) + toxic-nutritional (alcohol, hypovitaminosis, drugs,
toxic metals) + paraneoplastic + paraproteinemic (amyloidotic, gammopathies,
cryoglobulinemia) + in the course of collagen + hereditary diseases (Charcot-Marie-Tooth).
It is based on the clinical and instrumental finding of a functional deficit of
the peripheral nervous system. There is a "Diabetic neuropathy index" or DNI
whose protocol includes:
-
foot inspection
-
evaluation of Achillei reflexes
-
vibratory sensitivity to the two big toes with tuning fork
If the exam is negative, the inspections must be repeated annually
Furthermore, the instrumental technique of electromyography is opportune for the
confirmation of the diagnosis and for a more precise determination of the
severity of the peripheral nervous system compromise.
In DNI it is an effective and useful tool because it predicts the diagnosis of
neuropathy with an approximation of 79%.
The cornerstone of therapy is always adequate control of diabetes, as evidenced
by the DCCT and the Scandinavian studies ("Stockholm Study" and "Oslo Study"),
especially with aggressive diabetes therapy, ie with early insulin therapy.
UKPDS has shown that good metabolic control is equally effective in type 2
diabetes.
Therapy makes use of:
- analgesics (paracetamol, codeine, NSAIDs)
- tricyclic antidepressants (amitriptyline, imipramine, desipramine)
- anti-arrhythmics (mexiletine)
- capsaicin (chilli extract) for local use.
Some authors consider the role of gamma-linolenic acid as a component of the
phospholipid structure of the neuronal membrane present in lower concentration
in diabetics
- Alpha lipoic or thioctic acid with antioxidant effect
- Acetyl-carnitine
- Ace-inhibitors for their vasodilating action
- Still pregabalin and gabapentin
- vitamin B12