- THIS MATERIAL IS PUBLISHED AND PROTECTED BY U.S. COPYRIGHT LAW - REPRODUCTION PROHIBITED UNLESS FOR PERSONAL USE, EXCEPTING AUTHOR PERMISSION - NEUROPATHY and ARTHROPATHY IN THE INSENSITIVE FOOT PRESENTED IN FOUR PARTS PART TWO 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 were discussed. In this section, the various diagnostic modalities and clinical characteristics which assess the nature and extent of the neuropathies are presented. Section three will cover medical and surgical therapeutic measures relating to the specific nature of the neuropathic symptomatology. VASCULAR FINDINGS AND DIABETIC NEUROPATHY Vascular studies by the Doppler technique demonstrate that in a neuropathic leg the arteries are rigid and peripheral blood flow is increased and associated with arteriovenous shunting. Of significance are the profound vascular differences between the neuropathic and non- neuropathic diabetic patients. Those showing severe peripheral neuropathy show markedly abnormal blood velocity profiles. Medial wall calcification occurs almost exclusively in the neuropathic subjects. It is thought that while there is no overt evidence of peripheral arterial disease, the neuropathy may lead to disturbance in the blood flow which may be important in the etiology of the lesions which we associate with neuropathy, namely the neuropathic ulcer and the neuropathic joint. Diabetics having severe peripheral neuropathy show markedly increased resting flow as demonstrated by venous occlusion plethysmography, with a loss of a normally occurring spontaneous variations which depend on sympathetic activity. See table 2. Arteriograms show increased vascularity with rapid flow through dilated vessels feet and early filling of the venous circulation, which is evidence of abnormal arteriovenous shunting. It was noted a study by Nielson that the blood flow was abnormal in every neuropathic subject. In those with neuropathic joints there is a increase in diastolic flow as well as a sharp decrease in pressure from ankle to toe. These subjects show the characteristic lesions of a neuropathic foot, and it was suggested that the loss of the protective effect of pain was due to an abnormality of flow being an important etiological factor. The eventual osteoporotic rarefaction of bone is due to the arteriovenous shunting leading to increased venous pressure and abnormal bone cell activity. The foot is then even more susceptible to the normal biomechanical stresses that occur with the neuropathy with the eventual development of the neuroarthropathy.(25,26) The ankle-arm index has been of questionable value as far as its usefulness in clinical determination of arterial insufficiency in the diabetic. This is largely due to the wide variation in ankle-arm indexes due to vessel compressibility that results from vascular classification common in diabetics. However when the index is lower than 0.9 it can be assumed that there is a 95% certainty that there is an significant arterial insufficiency. Minimum pressure necessary for healing would be represented by an index of 0.45 with an average ankle pressure of 70mm Hg. A second exam may be performed testing for reactive hyperemia. A tourniquet is inflated on the leg for ten to fifteen minutes. Upon its release in a normal patient, a normal hyperemia of short duration will be seen. With patients having peripheral vascular disease, the leg muscles having been deprived of circulation, in addition to the decreased vascular flow, will divert more blood flow from the foot and ankle resulting in diminished ankle pressures. Quantitation of the initial resting pressures, the amount of pressure dropped, and the length of time until the pressure returns to normal, are indications of the degree of insufficiency.(27) PHYSICAL EXAM Symptoms are distal muscle weakness of lower extremities, spreading proximally, combined with hypersensitivity to light touch or pressure. In severe cases, wasting and atrophy of muscles may be noted. The skin may be atrophic and xerotic. Excessive perspiration of the palmar and plantar aspects is occasionally found. Upper motor symptomatology may be elicited by the exaggerated deep tendon reflexes initially, but are usually diminished and may be totally absent by the time of diagnosis. Paresthesias first are noted by the patient complaining of a numbness and tingling, or sensations of hot or cold temperatures in the feet. In more unusual cases, severe burning and shooting-type pains can occur in the absence of any other sign of neuropathy. Unlike Hansen's disease, this causalgia occurs associated with excessive perspiration and very little reflex change. It is referred to as "burning foot" syndrome and can also be associated with pantothenic acid deficiency. In patients with nutritional polyneuropathies, reduced blood levels of nicotinamide and nicotinic acid have also been seen.(37) CLINICAL FINDINGS OF CHARCOT JOINTS The patient presents with painless bone collapse in combination with a painless foot and ankle swelling, large plantar ulcers, and cellulitis. They usually have strong palpable pulses, warm feet and are good healers. The extent of the ulcer might be wide, with tension impeding its closure due to subdermal edema and fibrosis, combined with hyperostosis beneath it due to the subluxed joints. Oftentimes this will not allow the ulcer to close without surgical resection. Occasionally the skin may be erythematous and have an increased temperature making it difficult to distinguish from an infectious process. RADIOLOGIC FINDINGS OF CHARCOT JOINTS Radiologically two types of bony changes are usually seen resulting destructive type or Charcot joint, which predominates at the more proximal tarsal joints. The joint is anesthetia by due to peripheral nerve disease and relaxation of the joint capsule leads to talipes valgus and a severe destabilization of the intertarsal and tarsal metatarsal joints. The constant grinding and shearing results in fragmentation and infraction of the tarsal bones. Luxation, bizarre osteophyte proliferation, ankylosis, and sclerosis of the fragments is characteristic. Because of the severity of joint destruction it may be difficult to distinguish features due to infection from those due to the neuropathic defect and so infections which frequently supervene should be considered in the differential diagnosis. Distally, the atropic variety is the second type in the neuropathic joint picture, where the bone becomes resorptive or mutilated. This is confined to the forefoot and often appears in the metatarsal phalangeal joints assuming a narrowing of the epiphyseal shaft, which makes those joints have a pencil-in-cup appearance on X-ray. Oftentimes conspicuous subperiosteal proliferation is seen on the diaphysis resulting from pathologic fractures or secondary to trauma.(38,39,40) DIAGNOSTIC METHODS Laboratory blood studies will reveal an increased white cell count and increased erythrocyte sedimentation rate. The radiographic presentation is not dissimilar to that of osteomyelitis which must be ruled out. The differential is best determined clinically when the cellulitis and edema are brought under control and the increased white blood cell count and erythrocyte sedimentation rate return to normal. In the case of dirty-looking ulcers or those exhibiting perforation of considerable depth a sinogram is useful to determine the extent of the penetration should bone or joint capsule involvement be questioned.(39) Bilateral radiographs should always be considered even in cases of an asymptomatic contralateral foot because early neuropathic changes might be present in that foot. When the clinical or radiographic findings cannot distinguish between neuropathic osteoarthropathy and osteomyelitis, a bone biopsy should be considered. A synovial biopsy should also be considered as the incorporation of bone and cartilage fragments deep into the synovial membrane, a hallmark characteristic pathognomonic of the neuropathic joint. The differential for osteoarthritis is that bone and cartilage fragments are found just beneath the linings of the synovium in a synovial biopsy. X-ray studies of this skull and spine might be ordered to rule out syringomyelia, spinobifida, and myelomeningocele. This should only supplement a complete neurologic examination. Serologic laboratory tests may rule out pernicious anemia or tertiary tabes dorsalis. Pernicious anemia may be diagnosed initially from the complete blood count indices being a macrocytic, hypochromic anemia. Serum B12 should rule out, along with a Schilling's test using radioactively tagged cyanocobalamin, a lack of intrinsic factor production necessary for the absorption of vitamin B12. Nerve conduction studies should rule out peripheral nerve disorders, such as Charcot-Marie tooth disease. Serologic tests for rheumatoid arthritis, HLA testing for psoriatic arthritis, serum uric acid levels and joint fluid aspirates for gout and neoplasms should be considered. In order to rule out the diagnosis of the hematogenous form of osteomyelitis, technitium and combined gallium and technitium scans may be helpful on occasion. Technitium in the vascular phase would show reflection of increased blood flow to the area of bone. This is caused by an increase in vascularity caused by the hyperemia with vessel dilation and arteriovenous anastomosis with the venous congestion. The second phase or bone phase of the technitium scan occurs in the microcirculation of bone in the capillaries of the Haversian system where the isotopes contact the osteoid surface and bind to the hydroxyappatite crystals. A positive bone phase is significant of increased bone formation which can be a difficult differential from osteomyelitis being positive in the acute stages. Technitium, however, has its usefullness in detecting a significant number of silent lesions. It may be helpful in identifying active bone processes which have atrophic and hypertrophic processes. Gallium is incorporated into neutrophil lysosomes and for this reason is considered an inflammatory imaging agent. It is largely concentrated at the areas having increased vascular permeability, localized lysosomal enzymatic activity, and uptake directly into the bacteria. This presents a problem in patients with ulcers superficial to the sublux Charcot joint. Therefore distinction between skin and acute or chronic bone infection cannot be made with gallium. The best diagnosis still rests upon evaluation with bone biopsy and bone culture.(41) Temperature assessment in the insensitive foot can be a good method of early detection and monitoring damage. Thermography has been found to be useful in early diagnosis of neuropathic arthropathy in the feet of diabetics. A positive correlation is known between superficial temperature variation and static pressure on the weight-bearing areas of the human body. A difference in temperature greater than one degree centigrade is considered to be significant when making bilateral comparisons. Differences of up to six to eight degrees centigrade are often seen on the feet when an injury or inflammation is present. Treatment regimes that would distribute stress more evenly on the plantar aspect, such as molded shoes, should show a smaller change in temperature variation on the area. Changes in temperature during a conservative treatment regime might provide an important guide to the response of tissue to the treatment. Should a focal temperature difference increase, the area is probably receiving more stress than is tolerable. More homogeneous temperature variations would show that the treatment regime is successful. Polaroids photographs of thermograms may serve as a useful tool for patient education. Results recorded this way have an immediate impact, thus motivating the patient to better compliance in their ulcer therapy. Temperature readouts are instantaneous and may serve as useful feedback to concretely demonstrate to the physician if the therapy and is working or not.(42) The state-of-the-art diagnostic tool for patients with dysautonomias may be done by means of a skin vasomotor reflex using a laser doppler velocimetery. This measurement of capillary velocity shows that skin blood flow will fluctuate in response to various test stimuli and thus provide an index of arteriolar tone which is in turn determined by sympathetic nerve traffic. With the diabetic, certain test responses were altered or absent such as the inspiratory gasp stimuli and cold pressor test affect on the capillary blood velocity. Therefore skin blood flow changes provide a good, approximate index of sympathetic activity. The Mayo Peripheral Nerve Laboratories have found that these along with other tests provide a satisfactory search for distal and generalized impairment of sudomotor and vasomotor function.(43) See figure 3. END PART TWO SEE REFERENCES PART FOUR