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NEUROPATHY and ARTHROPATHY  
IN THE INSENSITIVE FOOT  
  
PRESENTED IN FOUR PARTS    
  
PART ONE  
  
Peter F. Kelly, D.P.M., F.A.C.F.A.S.  
  
Diplomate, American Board of Podiatric Surgery  
Fellow, American College of Foot and Ankle Surgeons  
  
TABLE OF CONTENTS  
  
PART ONE  
  
Abstract						     3  
Introduction						     4  
Summary of Development of the Neuropathic Joint 	     4  
The Progression of Joint Destructive Hyperlaxity	     5  
The Clinical Appearance of Diabetic Neuropathy		     8  
The Histochemical Basis of Diabetic Neuropathies	     10  
Hereditary Peripheral Neuropathies			     12  
Acquired Peripheral Neuropathies			     13  
The Ulcerative Neurotropic Foot 			     15  
  
PART TWO						     17  
  
Abstract						     18  
Vascular Findings in Diabetic Neuropathy		     19  
Physical Exam						     20  
Clinical Findings of Charcot Joints			     21  
Radiologic Findings of Charcot Joints			     21  
Diagnostic Methods					     22  
  
PART THREE						     26  
  
Abstract						     27  
Principles of Therapy					     28  
Surgical Management					     32  
Conservative Management 				     33  
Medical Management					     37  
Summary 						     38  
  
ABSTRACT  
     In the first of three parts of this paper, the more frequent etiologies of  
the various neuropathies causing arthropathies found in Podiatric  
Medicine are discussed.  A variety of diagnostic modalities exist, and  
those along with the clinical features assessing the nature and extent of  
the disease to the physician are presented in section two.  Section three  
covers medical and surgical therapeutic measures relating to the specific  
nature of the neuropathic symptomatology.   
  
INTRODUCTION  
  
     "The foot is the link between the person and the earth", stated Keith  
(1).  By this simple understanding of foot function is captured the entire  
basis of maintaining its integrity.    
  
     The patient having a neuropathic disease, has an unawareness of  
chronic and repeated trauma to usual motion and pressures.  In the  
insensitive foot, the neuropathy may vary from a mild loss of  
proprioception to complete anesthesia, motor loss, and autonomic  
nervous system involvement.  Metabolic complications precipitating the  
neuropathy may contribute directly to structural changes in the joint and  
the osseous supportive structure.  The patient is predisposed to a life of  
progressive ulcerative lesions, which result from degeneration and  
luxation of the joint creating the abnormal plantar pressures.    
  
     The importance of normal soft tissue health in the lower extremity  
has its basis in the proper biomechanical operation of the foot.  In  this  
regard, the foot specialist should understand that in maintaining foot  
health, that joint alignment is the biomechanical foundation, and to  
correct such deformities are as important as managing the underlying  
disease.  This is essential for the life of the limb, and the quality of life  
for their patient.(2,3)   
  
SUMMARY OF DEVELOPMENT OF THE NEUROPATHIC JOINT  
  
     The specific etiology of neurotropic arthropathies (NA), or Charcot's  
Joint, is a neuropathic degeneration to the motor and sensory fibers of  
the joint structures, which leads to a muscular unbalance combined with  
a loss of proprioception.  This is associated with a variety of pathologies  
such as diabetes, syphilitic tabes dorsalis, Hansen's disease,  
syringomyelia, myelomeningocele, trauma, nutritional disorders  
secondary to alcoholism, pernicious anemia, avitaminosis, and rarely  
congenital indifference to pain.(4,5)  
  
     A result of this loss of proprioception is the arthropathy and  
subluxation which has a direct implication on the health of soft tissues  
requiring proper positioning of the joints to sustain normal perfusion and  
weight distribution.  Shock absorption is highly dependent upon the  
cushioning effect of cartilage and synovial fluid.	This becomes  
markedly decreased when the lower extremity becomes involved with  
arthritis.  This results in microtrauma particularly to soft tissues which  
bear an increased pressure due to osseous subluxation.  An unbalanced  
muscular strength due to the neuropathy places pressure on perimetry of  
joint cartilage of luxed or subluxed joints creating excess wear, and  
distorting capsules maintaining alignment forming a vicious cycle  
toward its degeneration to an ankylosed state.	It could be said  
that "the patient's quality of life depends on the quality of their  
movement".(6)   
  
THE PROGRESSION OF JOINT DESTRUCTIVE HYPERLAXITY  
  
     Weight bearing produces stress along multiple vectors.  Repetitious  
compressive stresses, angulatory, tortional, and tensile stress, are applied  
in different proportions during normal daily activity.  The cellular and  
fiber alignment of cartilage, and the associated subchondral bone, is  
designed to optimally dissipate the uniaxial, compressive forces. 
	In cyclic loading and unloading the extremities are aligned to  
distribute stresses from one body segment to another.  The forces are  
largely uniaxial in nature and transmission of these forces will smoothly  
radiate through cartilage and subchondral bone with shock absorption  
well dissipated through the appropriate tensile elements.  
  
     For the health of the cartilage, cyclic loading is essential.  The  
periodic compression changes the charge within the proteoglycan matrix,  
causing it to perfuse water and its solutes. Cartilage in this respect  
behaves like an electrolytic solution, this uniaxial pressure causing what  
is known as the "electrokinetic effect".  Water is dependent upon this  
proper functioning, being eighty per cent of the total weight of  the  
cartilage, which functions to provide resiliency and frictionless  
movement.(7)   
  
     As long as the joint is functioning throughout its normal range of  
motion with normal periodic compressive stress in a normal alignment,  
there may be periarticular symptoms, but this will not contribute toward  
the destructive, degenerative changes.  This alignment will distribute  
proper weight along the weight-bearing surface and minimize the soft  
tissue damage.  However tortional and tangential loading are forces for  
which distribution patterns of cartilage and bone are not well adapted.   
Tangential forces are likely to cause microtears in the lamina splendins,  
the outermost layer of articulating hyaline cartilage.  Repeated activity  
can gouge out layers extending to the subchondral bone.  The limited  
ability of cartilage to repair itself approaches impossible under these  
conditions.(6,8)  
  
     Subjecting a malaligned joint to repeated use not only makes it  
unable to distribute forces of stress loading, but it affects the  
periarticular capsular tissues otherwise maintaining its functional  
position.  This contributes to predictable instability, and progression of  
the damage.  The malalignment of joints, soft tissue imbalances, or  
chronically applied outside forces, will not allow normal perfusion to  
occur to the chondrocytes, resulting in predictable effects on the  
cartilage substance.  
  
     Joint adaptation aggrivates soft tissue and muscular imbalances,  
increasing instability of that joint.  Ligamentous structures become lax  
and incompetent.  Also the asymmetrical loading will not allow  
metabolic products to escape into the synovial fluid.  Nutrients are not  
forced into the cartilage on the lightly articulated areas.  In these early  
stages, changes in the synovium may also be observed.(5,6,7)   
  
     Normally, because of the golgi tendon organ flexor-extensor reflex,  
the muscles performing actions across the joint will seek a balanced  
redistribution.  In the case of the neuropathic patient, the joint is  
subjected to uncontrolled excessive loads.  Joint bodies result from the  
formation of detached pieces of articular cartilage, small osteoarticular  
fracture fragments, debris, or marginal osteophytes beginning at the  
articular margins and meshed within the synovium, hence known as the  
"stage of development".  Nourished by the synovial fluid, they grow  
slowly by the accretion of layers of cartilage on their surface.   
Fibrocartilagenous changes and calcification occurs on the cartilage  
component, but will not become bone as it still lacks a blood supply.    
      The primary change is in the yellow, scored, and denuded articular  
cartilage.  When cartilage is denuded blood vessels reach the surface  
from the subchondral bone directly beneath, and there is a localized  
advance in the line of ossification causing marginal and bizarre exostosis  
to develop around the periphery.  These impose upon the nerve endings  
of the synovium which would cause pain in the normosensitive, but in  
the neuropathy only and a reactive hyperplasia due to the irritation is  
seen.  Foci of fibrous tissues develop in the subchondral bone which  
continues to degenerate, seen as a cystic softening on X-rays.   
Subchondral bone may become more sclerotic and brittle, prone to  
fractures.  Free microscopic fragments	are absorbed by the  
adjacent joint structures, and the larger ones group together in this "stage  
of coalescence".  Gross evidence of cartilage and bone debris embedded  
within the synovium is pathognomonic of a Charcot's Joint.(11)  
  
      Because of the decreased sensation to pain, the continued paralysis  
and overuse of muscles distorting joint alignment results in a debilitated,  
progressively destablized situation, where the bone ends become  
sclerosed and ankylosed, and the extensive remodeling now sets the  
stage for the chronic septic ulcers of a functionless, broken down  
foot.(10,12)  
  
THE CLINICAL APPEARANCE OF DIABETIC NEUROPATHY  
  
     The manifestations of foot deformities in the diabetic result from a  
threefold neuropathic development.  First of all, foot deformities are due  
to a motor deficit.  Secondly, sensory impairement leads to anesthesia.   
Thirdly, from an autonomic dysfunction there is an increased  
susceptibility to sepsis.  It should be noted that while a significant  
number of control patients show clinically demonstrable neuropathy, a  
significant number of these patients do not necessarily develop a foot  
lesion.(13)   
  
     The incidence of neuropathy is common in diabetic patients, both  
symptomatic and asymptomatic.  In a study by Appleberg, et al., no  
significant difference between a collective group of diabetics generally  
classified as having foot lesions and the control group of diabetics and  
was found.  The neuropathy was almost as common in patients showing  
general outward physical manifestations of the disease as the control  
group.  However, when diabetic patients presented only the ulcers or  
septic lesions, the incidence of neuropathy was generally more  
common.(13)  See table 1.    
  
     Diabetic foot lesions typically fall into one of three categories.  These  
are the septic lesion, the ulcer, and the ischemic lesion.  Although these  
are usually distinct in etiology there is some degree of overlap in certain  
cases.  With regards to the ulcerative category, there are major factors  
responsible for the development of these lesions.  These factors include  
peripheral neuropathy which may involve both autonomic, motor and  
sensory nerves, microangiopathy, hypercoagulability of the blood due to  
changes in the glycosylated platelets or red cells and connective tissue  
abnormalities also related to glycosylation of collagen.  Are factors  
which promote stasis, instability of the foot, and a foot that is susceptible  
to varying degrees of minor trauma. (14,15,16)  
  
    The most common manifestations of neuropathies in diabetics include  
multiple manifestations of paresthesias, pain or numbness, and  
hypoesthesia.  Other earlier signs include a diminution of vibratory, light  
touch and sharp dull differentiation.  Deep tendon reflexes may also be  
decreased.   
  
      Orthopedically, an intrinsic muscular atrophy leads to hammer digit  
syndrome, prominant extensor tendons and an anterior shift in the  
plantar fat pad, with atrophy of the pad, and subcutaneous exposure of  
the metatarsal heads.  In addition to the sensory neuropathy, is an  
autonomic autosympathectomy resulting in an anhydrotic and diffusely  
hyperkeratotic plantar aspect.  This hard, dry and brittle skin is subject to  
frequent cracks and infections.  Neuropathic motor nerve involvements  
may cause changes in the joints creating a neuropathic or Charcot's joint,  
most often occurring at the foot and ankle and lesser tarsus.(17)     
  
     Clinically the cycle of neuropathy which results is the loss of joint  
sensation and a persistant and repeated trauma from weight bearing and      
results in a "Charcot foot" which appears swollen, club-like,  
erythematous and warm.  Radiologically, these feet are osteoporotic and  
ankylosed most frequently in the midtarsal, tarsal-metatarsal, lesser  
tarsus, and least frequently in the metatarsophalangeal area.  Exostosis  
on proximal and     distal aspects of the ankylosis how bizarre  
conformation impinging on soft tissue which is hypertrophic and  
edematous, showing old fibrosis secondary to chronic inflammation  
which is responsible for the local ischemia and	 chronic ulcerative  
breakdown.	See figure 2.	  
  
     The radiologic changes are generally similar to those seen in  
osteoarthritis (OA) of non-neurotropic origin.  Differentiating this from  
NA is generally the exaggerated degree of otherwise similar changes  
observed.(1)   
  
THE HISTOCHEMICAL BASIS OF DIABETIC NEUROPATHIES  
  
      Basically all forms of this disease may be related to abnormalities in  
vessels of different sizes or in the microenvironments of the nerves.    
Several types exist.  The diffuse form has two varieties called the diffuse  
large fiber disease (ataxic form), and a distal small fiber disease  
(hyperalgesic-autonomic form).  In the diffuse neuropathic diseases, an  
increased glucose level will have a significant effect upon the metabolic  
abnormality of nerve and Schwann cells.	The focal diseases reflect  
small vessel pathologic changes.  Other types are the polyradiculopathy  
and the mononeuritis multiplex (cranial nerve palsies, diabetic  
amyotrophy).    
  
      In animal models it has been shown that these abnormalities of nerve  
conduction velocity are not necessarily reversed by the administration of  
insulin once they have been established.  The conduction abnormalities  
are accompanied by axonal shrinkage which seem to be related to the  
intravenous level of glucose, suggesting that perhaps certain accute  
changes may even occur as a result of a production of interstitial  
hyperosmolarity.  These results are found in addition to the chronic  
changes which result from the long-term metabolic abnormality.  These  
may be related to glycosylation of proteins and the depositions of  
monosaccharides intercellularly.  
  
      Clinical evidence of neuropathy is the hyperglycemia which has been  
shown to contribute to the   
impairement of peripheral nerve conduction.  This has been shown to  
have a direct relationship to the severity of hyperglycemia.  Infrequently  
in measurements of abnormal peripheral nerve function of  
hyperglycemic diabetic patients, it is observed they improve over a time  
of weeks or months with concomitantly improved blood glucose  
control.(18,19)  
  
     Recent experimental studies point to the cause of peripheral nerve  
degeneration in diabetics as being due to abnormalities of axonal  
transport.  Normally in nerve cells newly synthesized proteins are  
rapidly transported to the distal parts of the cell and undergo a process of  
turnaround by which they are carried back to the cell bodies for  
degredation.  The purpose of this retrograde transport which is  
independent of the direction of impulse traffic and serves multiple  
purposes.  Most significant are for transport of nerve growth factor to  
reach their targets from the regional nuclei, to recirculate surplus  
materials which are in access of local need in the distal region, and as an  
essential step in the process whereby worn out organelles and membrane  
constituents are transferred to the lysosomes of the perinuclear region for  
ultimate digestion and disposal.  Since the cell bodies are essentially the  
sole site for assembly of neuronal proteins and organelles, it is obvious  
why defective transport has received such attention as a possible cause  
of peripheral nerve disease.    
  
     In the early event of peripheral nerve disease, it may be that more  
subtle disturbances of this transport process contribute to the  
development of peripheral neuropathies.  In peripheral nerve disease of  
diabetic origin the nerves carry less than the normal amount of  
retrogradedly transported pulse-labelled glycoprotein.  The early  
appearance of this defect suggest that the impaired turnaround of this  
rapidly transported material in the distal axon could be the trigger that  
initiates the chain of events leading eventually to the characteristic  
neuropathy of human diabetes.  Streptozocin-induced diabetes has been  
demonstrated to act at the turnaround distal portion.	This turnaround  
defect is reversed by treatment with insulin.(20)    
  
    There is a second problem in axonal transport in nerves of diabetics,  
which is a reduced velocity in the slowest phase of anterograde  
transport.  This slow transport delivers the neurofilament proteins  
believed to maintain axonal diameter.  This may be an explanation to the  
well-known shrinkage of myelinated axons.(21)  See Figure 1.    
  
     In addition to intravascular and interstitial glucose levels, other  
factors of diabetic neuropathy must be considered.  Such are levels  
circulating lipids, actions of insulin other than modifying blood glucose  
levels, destruction and condition of the myelin sheath, energy  
metabolism of the peripheral nerve, and morphologic changes in the  
large or small blood vessels supplying the peripheral nerves.(22)  A  
significant derangement of the myoinositol metabolism is thought to be  
an active contributor in the diabetic peripheral neuropathy in addition to  
absolute lack of endogenous insulin and changes in enzymatic activity. 
	The myoinositol is incorporated in the lipid  
phosphatidylinositol, and the decrease associated with free myoinositol  
levels is associated with the decrease in motor nerve conduction velocity  
in animal models with diabetes.	If free myoinositol nerve levels are  
restored to normal values impaired motor nerve conduction velocities  
are prevented despite hyperglycemia and high concentrations of the  
polyol path metabolites, such as sorbitol and fructose.(23,24)    
  
HEREDITARY PERIPHERAL NEUROPATHIES  
  
     The metabolic and congenitally based peripheral lesions are too  
comprehensive a subject to be covered within the scope of this article.   
However the lesions that are most likely to affect the biomechanical  
aspects of walking would be those that would begin distally in the lower  
extremities and progressed proximally.  Hereditary sensory radicular  
neuropathy is such an example.  This neuropathy has a sporadic and  
familial form as well as the hereditary type.  As with many congenital  
neuropathies, inheritance in siblings appears to be autosomal-dominant.   
Other family members may be undiagnosed of the disease, but  
acknowledge that foot ulcers are "inherited" in their family.  By early  
recognition of this disease and removing pressure from the involved  
areas, or by spreading pressure equally over the foot with proper  
footwear, ulcers are preventable.(32)    
  
     Neurotropic arthropathy may also be caused by Dominantly Inherited  
Sensory Neuropathy and may be associated with painless plantar ulcers,	    
mutilating acropathy, and severe distal sensory loss.  The only  
manifestation of DISN may be "burning feet" syndrome.  Generally as  
the history, these patients have also had severe sensory loss over the  
toes, feet, and distal regions of leg and have had distal ulcers and other  
evidence of mutilating acropathy.  Symptoms begin at a characteristic  
age for hereditary sensory neuropathy and sural nerve biopsy reveals  
mild changes typical to the change seen in inherited neuropathy.   
Relatives which have "burning feet" and mild neuropathic findings show  
a autosomal-dominant pattern.    
  
     Burning pain is related to the neuropathic process that is suggested by  
several factors.  Positive symptoms are due to the presence of ectopic  
generators in the damaged peripheral nerve.  This involves alterations in  
the nerve membrane and in its environment.  The ectopic generator is  
most readily produced by small Wallerian degeneration, but neuralgias  
can also result from demyelination.(33)    
  
ACQUIRED PERIPHERAL NEUROPATHIES  
  
     When perforating ulcerations of the foot undergo rapid evolution of  
the cutaneous and bone lesions, a severe tarsal tunnel syndrome should  
be ruled out.  The extent and progression of the ulcers can be so severe  
that partial forefoot amputations seem to be otherwise indicated to the  
general medical practitioner unfamiliar with the etiology of severe  
posterior tibial nerve compressions.  Such can be diagnosed with a  
posterior tibial nerve neurography.  An interfascicular neurolysis of the  
nerve at the level of the tarsal tunnel would provide a much better  
alternative as a surgical intervention.  It should be kept in mind that with  
a tarsal tunnel syndrome of this magnitude a bilateral periarterial  
sympathectomy might be necessary in conjunciton with the above- 
mentioned surgical procedure.(34)    
  
     Other causes of neuropathic arthropathy may be secondary to severe  
degenerative spinal diseases.  Secondary to severe degenerative spinal  
diseases, the diagnosis rests largely in the findings of unilateral  
dermatome deficits.  The best comparisons can be made with those  
patients whose localized damage to nerve roots or peripheral nerves is  
associated with this phenomena.  
  
	Radiologic association and operative findings will point to  
nerve root pressure as the primary problem.  Although degenerative 
	disc disease and lumbar spondylosis is very common and may  
produce nerve root pressure and radiculopathies, a neuropathic osseous  
degeneration exhibits a unique combination of features:  1. It is  
extensive occurring at several adjacent levels, 2. it is incomplete, and 3.  
it is unilateral and confined.  
  
	To explain, should the deficits be to roots L3 to S2, a  
diminution of sensation of the entire foot similar to a diabetic or other  
peripheral neuropathy would be presented along with the disc  
syndromes.  In most cases the patient's neurologic deficit is incomplete  
and so perception of pain in the affected joints and preservation of motor  
power may be demonstrated.  Therefore because the patient is usually  
ambulatory they would subject their foot to the stresses necessary for the  
development of the arthropathy.  A neuropathic osteoarthropathy would  
not usually be seen in the setting of motor paralysis unless the area  
involved was subject to vigorous passive motion.(35,36)   
  
ULCERATIVE NEUROTROPIC FOOT  
  
     In the many complications of the neurotropic foot, plantar ulcerations  
are the most common and can be a pronounced problem in areas of low  
socioeconomic status where poor hygiene and neglect is common. 
	The causes of insensitive feet is by nerve damage to the skin or  
peripheral nerve trunks.  Oftentimes the patient will not seek medical  
attention because the ulcerative site is not painful.  
  
     Two major factors, insensitivity and biomechanical factors, play the   
major the roles in accentuating the process of tarsal disintegration in the  
neuropathic foot.  The biomechanical factors predominate secondary due  
resulting in a change upon the weight bearing areas and weight  
transmission lines.  Other factors such as the loss of protective reflex,  
infection and infiltration of bones, are also considerations in lesion  
development.(28)  
  
     The greatest single predisposing preulcerative lesion of plantar ulcer  
development is a hyperkeratosis.  These diffused callusities are  
secondary to an autonomic autosympathectomy which results in damage  
to the nerve fibers of the apocrine sweat glands.  The resulting  
anhydrotic skin is hard and brittle, predisposed to fissuring and eventual  
ulceration.  The skin lesions will subside with adequate therapy and  
usually do not result in much disability per se.(29)	  
  
     There is also an increased incidence of malignant skin tumors in  
patients with chronic ulcers.  It is well known to surgeons and others that  
chronic ulceration occasionally gives rise to malignant change, and  
although not as rare as the literature would suggest.  Complications are  
commoner if the examiners would take time to look for these  
developments in patients with long-standing lesions.(30,31)	  
  
     Squamous cell carcinoma is estimated to occur in nine per cent of  
'tropical' or 'phagedenic' ulcers.  Ulcers undergoing malignant  
degeneration tend to produce a fungating mass within the initial stages  
with only a radiologically nonspecific periosteal reaction.  In later stages  
the lesion appears punched-out in the bone.  The malignant degeneration  
in a plantar ulcer should be specifically investagated or else it is likely  
will remain undiagnosed for a considerable time.  This is because the  
ulcerated foot not only sequestrates the tissue before the malignancy  
becomes obvious, but also because the area has a poor blood supply and  
does not readily support the growth of malignant tissue otherwise  
changing the gross morphology.    
  
     Metastasies occur slowly, but positive clinical findings of enlarged  
lymph nodes should not be followed up by excision or biopsy.	An  
attempt to do so will produce a chronic fistulating lesion at the biopsy  
site.  Once the primary focus in the ulcer has been safely removed, the  
septic lymph nodes will settle down and any metastasies diminish in size,  
and in some cases disappear.(31)   
  
END PART ONE  
  
SEE REFERENCES PART FOUR