Artropatie Charcot

Artropatia Charcot, sau osteoartropatia neuropatică evolutivă, cunoscută și ca neuroartropatie, ori articulație (sau picior) Charcot, este o maladie degenerativă a articulațiilor piciorului, azi întâlnită aproape exclusiv la bolnavii de diabet zaharat afectați de polineuropatie (una din complicațiile “tardive” ale diabetului), materializată prin distrugere și deformare osoasă la nivelul articulațiilor gleznei (tibio-talară), tarso-metararsiene și metatarso-falangiene). A nu fi confundată cu "neuropatia Charcot–Marie–Tooth", o maladie sistemică și ereditară cu origine în defecte genetice și cromozomiale. Neuro-artropatia Charcot este o boală cronică care nediagnosticată și tratată la timp, conduce la infirmitate (prin deformarea arhitecturii osoase a picioarului sau/și anchiloză articulară), la amputări și posibil chiar deces (ca urmare a ulcerațiilor plantare și infecțiilor). Odată ce procesul inflamatoriu și degenerativ a fost amorsat, maladia nu mai poate fi vindecată, iar prin tratament evoluția bolii nu poate fi decât în cel mai bun caz încetinită.^[1]^[2]

Istoric

Artropatia Charcot a fost observată pentru prima dată de către medicul francez Jean-Martin Charcot la pacienții afectați de complicațiile neurologice ale sifilisului. Și-a făcut cunoscute observațiile în publicații de specialitate în 1868. Neuroartropatia Charcot apare întotdeauna în urma unei neuropatii periferice. Ulterior s-a arătat că boala apare drept complicație și a altor maladii, factorul comun care le leagă însă pe toate, fiind polineuropatia periferică.

Patogenză

Maladia are o dublă cauzalitate: în primul rând se datorează pierderii funcționalității fibrelor nervoase simpatice^[3]^[4]. Ca parte a sistemului nervos autonom, acestea sunt implicate în reglarea debitului sanguin periferic.^[5] O creștere a debitului sanguin periferic la bolnavul de neuropatie diabetică duce la “spălarea” (adică antrenarea în sistemul circulator) mineralelor^[6] de pe eșafodajul de colagen din oase, fapt care fragilizează structura osoasă^[7]. În patogeneză este implicată însă și afectarea nervilor senzitivi, prin pierderea sensibilității (la durere), însoțită de pierderea funcționalității sistemului de percepție a poziției oaselor piciorului (sistemul proprioceptor). Lipsa de senzație (durere) distruge în timp comportamentul preventiv (ca la cei cu analgezie congenitală^⁠(en)^[traduceți]), traumele și fracturile acumulându-se peste traume și fracturi, până la infirmitate și ulcer. În mod similar, pierderea sistemului proprioceptor face ca creierul să nu fie informat în fiecare moment (și astfel nu mai acționează în consecință) de poziția oaselor în articulații), fapt care duce la instabilitate, și astfel la risc de traumă și fracturi repetate.

La pacientul diabetic traseul patologic este acesta: Hiperglicemia cronică distruge fibra nervoasă prin glicolizarea proteinelor, care astfel își pierd conformația și deci funcția; o altă cale prin care hiperglicemia atacă (indirect) fibra nervoasă este afectarea microvasculară (prin activarea căii metabolice poliol, cu produșii toxici sorbitol și fructoză), care duce la reducerea fluxului de oxigen și nutrienți spre fibrele nervoase; la diabeticul tip I este posibilă și o implicare autoimună în inflamația și atacul fibrelor nervoase.

Odată instalată, neuropatia va antrena prin cele 2 (posibile) căi, anume vasodilatația masivă a piciorului și hiperemia locală (promovată ca explicație de școala de medicină franceză) și traumatismul (teoria neurotraumatică, promovată ca explicație de școala germană de medicină; teoria neurotraumatică nu explică însă apariția artropatiei Charcot la persoanele cu neuropatie imobilizate la pat - paraliticii, de ex., care sporadic dezvoltă și ei această maladie, sau pacienții diabetici la care aparatul locomotor nu este pus, din diverse motive, niciodată sau doar rareori în sarcină (masă corporală pe membrele inferioare) - dovadă că etiologic vorbind a.C. este multifactorială, iar cauzalitatea neurotraumatică nu pare a fi singură capabilă să provoace boala), provoacă o distrugere a arhitecturii piciorului.^[8]

Teoria neurovasculară s-a dovedit a fi mai simplu de verificat: la un pacient cu a.C. diagnosticată, dar care la un moment dat a dezvoltat o arterioscleroză ocluzivă (obliterans), artropatia a încetat să evolueze pe toată perioada dinaintea revascularizării membrului afectat de ischemie. Evoluția a.C. încetează deci dacă hiperemia locală este, cumva, eliminată. Conform acestei teorii, afectați de diabet fiind, nervii care comandă musculatura micilor artere ale piciorului nu-și mai îndeplinesc funcția (care asigură vasoconstricția); vasele sunt astfel permanent relaxate (la fel, glandele sudoripare nu mai pot evacua secreția ptr. că musculatura nu mai este stimulată de nervii distruși: pielea și unghiile piciorului devin uscate și se îngroasă), fapt care permite continuu existența unui flux sanguin intens prin extremitatea membrului inferior.

Din cauza hiperemiei^[9] cronice structura osului se fragilizează: mineralele sunt spălate (washed-out) de pe scheletul colagen; osul fragilizat al unui membru deja insensibil (neuropatic) va fini prin a se fractura; procesul reparatoriu amorsat va fi însă vicios: este foarte viguros, însă ineficient, pentru că o dată în plus producția de fibre organice pentru eșafodaj nu este dublată de o mineralizare tot atât de eficace; nu există astfel o depunere pe măsură a mineralelor pe scheletul proteic; porțiunea reparată va fi deci tot atât de fragilă ca restul osului. Pacientul produce din belșug os nou în zona fracturii, dar care fragil fiind, este el însuși susceptibil de a se refractura dacă este supus sarcinilor. În plus, feed-back-ul senzorial, care la individul normal permite ca remodelarea osoasă să se producă de-a lungul liniilor de stres, este absent (neuropatie), zona reparată rămânând indefinit deformată și masivă; aceleași defecte senzoriale produc un dezechilibru și între activitatea de resorbție (osteoclastică) și aceea de producție osoasă (osteoblastică).^[10]^[11]

Prevalență

Prevalența indicată în literatura medicală variază considerabil de la o sursă la alta; aprecieri relativ recente (Oloff, Musculoskeletal Disorders of the Lower Extremities, 1994; Diabetic Foot, Veves et al., 2006) susțin că unul din 10 diabetici va fi afectat la un moment dat de a.C., în timp ce la diabeticii care au dezvoltat deja polineuropatie periferică, unul din 3 va dezvoltă a.C.^[12] În "Evidence-based Orthopedics" ("Evidence-Based Medicine" series) editată de Mohit Bhandari se afirmă că a.C. are o pevalență atât în SUA cât și în restul lumii situată între 0.3% și 3% din populația diabetică.

Tratament

Tratamentul constă în repaus total al aparatului locomotor; scoaterea, un timp îndelungat (în medie 6 luni), prin diverse metode (ghips, gheată ortopedică din plastic, repaus la pat), din sarcină a piciorului afectat, este esențială pentru tranziția din faza inflamatorie în faza stabilizată.^[13] Deși osteoliza afectează adesea, prin extinderea procesului inflamatoriu, falangele vecine celei fracturate, lăsând practic largi porțiuni de structură osoasă lipsă (fapt care la vindecare participă la (sub-)luxația (dislocarea articulară) și proasta realiniere osoasă tipică piciorului Charcot, intervențiile de chirurgie ortopedică sunt în general excluse, pentru că actul chirurgical însuși poate reprezenta un factor declanșator al proceselor inflamatorii caracteristice afecțiunii. În anumite cazuri (echinism; sau o deformare a piciorului medial care implică prăbușirea boltei) se practica stabilizarea articulației prin fuziune. În faza stabilizată, se recomandă gheată ortopedică mulată. Recent, s-a descoperit că tratamentele cu antioxidanți ameliorează durerile. De asemenea, compania Pharnext a efectuat studii clinice pentru tratamentul cu numele de cod PXT3003.^[14]

Note

^ "Charcot foot (neuropathic osteoarthropathy) can be defined as a noninfectious and progressive condition of single or multiple joints characterized by joint dislocation, pathological fractures, and severe destruction of the pedal architecture which is closely associated with peripheral neuropathy (2,9,16)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 270
^ "The actual pathogenesis of Charcot arthropathy most likely is a combined effect of both the neurovascular and neurotraumatic theories (14,18,28,29,23). It is generally accepted that trauma superimposed on a well perfused but severely neuropathic extremity can precipitate the development of an acute Charcot foot. The presence of sensory neuropathy renders the patient unaware of the initial precipitating trauma and often profound osseous destruction taking place during ambulation. The concomitant autonomic neuropathy with its associated osteopenia and relative weakness of the bone predisposes it to fracture (20,26). A vicious cycle then ensues in which the insensate patient continues to walk on the injured foot, thereby allowing further damage to occur (9,13,14). With added trauma and fractures in the face of an abundant hyperemic response to injury, marked swelling soon follows. Capsular and ligamentous distension or rupture is also a part of this process and leads to the typical joint subluxations and loss of normal pedal architecture culminating in the classic rocker-bottom Charcot foot. The amount of joint destruction and deformity which results is highly dependent on the time at which the proper diagnosis is made and when nonweight-bearing immobilization is begun (9)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271
^ "We are therefore left with the inescapable conclusion that all the autonomic nerve fibers to the blood vessels of the lower extremity are sympathetic nerve fibers." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204
^ "The primary risk factors for this potentially limb threatening deformity are the presence of dense peripheral neuropathy, normal circulation and a history of preceding trauma, often minor in nature (4,13,18). " - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 270
^ "[…] some basic information regarding the autonomic nervous system control of blood flow through peripheral (extremity) blood vessels." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204
^ "The neuropathy wipes out the sensory and sympathetic nerves of the foot. As a result, the bones of the foot become soft and fracture. The ensuing repair process is exuberant but ineffectual, because the abnormally increased arterial flow allows for significant collagen scaffolding without adequate mineralization." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204
^ "This increase in blood flow allows for a "washing-out" and softening of the bones, and it is this increase in the blood flow that allows for a massive attempt to repair after each of the fractures." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.205
^ "Although the exact pathogenesis may vary from patient to patient, it is undoubtedly multifactorial in nature (2,10,14,18). The neurotraumatic (German) theory has tradi-tionally been proposed as the primary etiology of osteoarthropathy in which neuropa-thy and repeated trauma produce eventual joint destruction. The loss or diminution of protective sensation allows repetitive micro or macrotrauma producing intracapsular effusions, ligamentous laxity, and joint instability. With continued use of the injured extremity further degeneration ensues and eventually results in a Charcot joint. Underlying sensory neuropathy resulting from any disorder, is therefore a prerequisite under this theory of pathogenesis. However, the neurotraumatic theory does not explain all accounts of Charcot arthropathy, especially its occurrence in bedridden patients (2,4,9–11,13). " - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271
^ "The following clinical question must be addressed: If the Charcot's arthropathy is due to sympathetic denervation, which results in a localized hyperemia of bone, and if the hyperemia produces a localized demineralization of bone, which results in fracture fragmentation of the bone with weightbearing, then why would the Charcot's arthropathy stop after fusion (with or without tendon lengthening)?" - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.206
^ "In addition, the normal sensory feedback information that allows bone remodeling to occur along lines of stress is absent, resulting in a piece of bone that becomes very soft and that fracures under the pressure of weightbearing. The patient forms an excessive amount of new bone at the fracture site. This new bone also fracture, owing to the inadequate mineralization. However, the new bone formed at the fracture site fails to be remodeled, so that the initial site remains massively deformed." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204/205
^ "The neurovascular reflex (French) theory, in contrast, proposes that increased peripheral blood flow owing to autonomic neuropathy that leads to hyperemic bone resorption (19). This theory might indeed correspond to Charcot's original hypothesis of a central "nutritional" defect, although we now recognize this process as a peripheral nerve disor-der. Autonomic neuropathy (and endothelial dysfunction) results in an impairment of vascular smooth muscle tone and consequently produces a vasodilatory condition in the small arteries of the distal extremities (20,21). Impairment of neurogenic vascular responses in patients with diabetic neuropathy has been supported by one study that consequently also showed preserved maximal hyperemic responses to skin heating in patients with Charcot arthropathy (22). In concert with associated arteriovenous shunting there is a demonstrable increase in bone blood flow in the neuropathic limb. The resultant osteolysis, demineralization, and weakening of bone can predispose to the development of neuro-osteoarthropathy (2,18-20,23,24). Several studies have demonstrated reduced bone mineral density with an apparent imbalance between the normally linked bone resorption and production in patients with osteoarthropathy (25-27). Specifically, greater osteoclastic than osteoblastic activity has been noted in acute neuroarthropathy, suggest-ing an explanation for the excessive bone resorption during the acute stage (20,25)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271/272
^ "Subsequently, Bailey and Root, in their 1947 series, noted that 1 in 1100 patients with diabetes mellitus developed neurogenic osteoarthropathy (7). In the classic 1972 Joslin Clinic review of 68,000 patients by Sinha et al. (8), 101 patients were encountered with diabetic Charcot feet. This ratio of 1 case in 680 patients with diabetes brought greater attention to this dis-order and characterized the affected patients’ clinical and radiographic presentations. In the subsequent 30 years, there has been a significant increase in the number of reports on diabetic osteoarthropathy, its complications, and management (6–10).The prevalence of this condition is highly variable, ranging from 0.15% of all patients with diabetes to as high as 29% in a population of only neuropathic diabetic subjects (2,8,10,11). Recently, a prospective study of a large group of diabetic patients from Texas reported an incidence of 8.5/1000 per year. Neuroarthropathy was significantly more common in Caucasians than in Mexican Americans. (11.7/1000 vs 6.4/1000) (12). Although this study may give us better insight into the true frequency of osteoarthropathy in diabetes, much of the data we currently rely on are based on retrospective studies of small single center cohorts. Nonetheless, the incidence of Charcot cases reported is very likely an underestimation because many cases go undetected, especially in the early states (2,11,13).The frequency of diagnosis of the diabetic Charcot foot appears to be increasing as a result of increased awareness of its signs and symptoms (14). Although the original descriptions of neuropathic osteoarthropathy were attributed to patients with tertiary syphilis, diabetes mellitus has now become the disease most often associated with this severe foot disorder. Not only are diabetic patients with Charcot foot deformities at greater risk of amputation than those with neuropathic ulcers without osteoarthropathy, a study from the United Kingdom has also found them to have a higher mortality (15)". - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p.268/270
^ ""The treatment of Charcot arthropathy is not yet well defined. Treatment had been limited to orthotic/molded shoe support, cast immobilization with varying periods of non-weightbearing and surgical débridement." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.206
^ „Boala Charcot - Marie - Tooth! Cum sa vindeci boala in 2022?”. Boala Charcot - Marie - Tooth! Cum sa vindeci boala in 2022? ~ "Fii lumina acolo unde esti !". Accesat în 10 februarie 2022.

[1] "Charcot foot (neuropathic osteoarthropathy) can be defined as a noninfectious and progressive condition of single or multiple joints characterized by joint dislocation, pathological fractures, and severe destruction of the pedal architecture which is closely associated with peripheral neuropathy (2,9,16)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 270

[2] "The actual pathogenesis of Charcot arthropathy most likely is a combined effect of both the neurovascular and neurotraumatic theories (14,18,28,29,23). It is generally accepted that trauma superimposed on a well perfused but severely neuropathic extremity can precipitate the development of an acute Charcot foot. The presence of sensory neuropathy renders the patient unaware of the initial precipitating trauma and often profound osseous destruction taking place during ambulation. The concomitant autonomic neuropathy with its associated osteopenia and relative weakness of the bone predisposes it to fracture (20,26). A vicious cycle then ensues in which the insensate patient continues to walk on the injured foot, thereby allowing further damage to occur (9,13,14). With added trauma and fractures in the face of an abundant hyperemic response to injury, marked swelling soon follows. Capsular and ligamentous distension or rupture is also a part of this process and leads to the typical joint subluxations and loss of normal pedal architecture culminating in the classic rocker-bottom Charcot foot. The amount of joint destruction and deformity which results is highly dependent on the time at which the proper diagnosis is made and when nonweight-bearing immobilization is begun (9)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271

[3] "We are therefore left with the inescapable conclusion that all the autonomic nerve fibers to the blood vessels of the lower extremity are sympathetic nerve fibers." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204

[4] "The primary risk factors for this potentially limb threatening deformity are the presence of dense peripheral neuropathy, normal circulation and a history of preceding trauma, often minor in nature (4,13,18). " - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 270

[5] "[…] some basic information regarding the autonomic nervous system control of blood flow through peripheral (extremity) blood vessels." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204

[6] "The neuropathy wipes out the sensory and sympathetic nerves of the foot. As a result, the bones of the foot become soft and fracture. The ensuing repair process is exuberant but ineffectual, because the abnormally increased arterial flow allows for significant collagen scaffolding without adequate mineralization." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204

[7] "This increase in blood flow allows for a "washing-out" and softening of the bones, and it is this increase in the blood flow that allows for a massive attempt to repair after each of the fractures." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.205

[8] "Although the exact pathogenesis may vary from patient to patient, it is undoubtedly multifactorial in nature (2,10,14,18). The neurotraumatic (German) theory has tradi-tionally been proposed as the primary etiology of osteoarthropathy in which neuropa-thy and repeated trauma produce eventual joint destruction. The loss or diminution of protective sensation allows repetitive micro or macrotrauma producing intracapsular effusions, ligamentous laxity, and joint instability. With continued use of the injured extremity further degeneration ensues and eventually results in a Charcot joint. Underlying sensory neuropathy resulting from any disorder, is therefore a prerequisite under this theory of pathogenesis. However, the neurotraumatic theory does not explain all accounts of Charcot arthropathy, especially its occurrence in bedridden patients (2,4,9–11,13). " - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271

[9] "The following clinical question must be addressed: If the Charcot's arthropathy is due to sympathetic denervation, which results in a localized hyperemia of bone, and if the hyperemia produces a localized demineralization of bone, which results in fracture fragmentation of the bone with weightbearing, then why would the Charcot's arthropathy stop after fusion (with or without tendon lengthening)?" - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.206

[10] "In addition, the normal sensory feedback information that allows bone remodeling to occur along lines of stress is absent, resulting in a piece of bone that becomes very soft and that fracures under the pressure of weightbearing. The patient forms an excessive amount of new bone at the fracture site. This new bone also fracture, owing to the inadequate mineralization. However, the new bone formed at the fracture site fails to be remodeled, so that the initial site remains massively deformed." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.204/205

[11] "The neurovascular reflex (French) theory, in contrast, proposes that increased peripheral blood flow owing to autonomic neuropathy that leads to hyperemic bone resorption (19). This theory might indeed correspond to Charcot's original hypothesis of a central "nutritional" defect, although we now recognize this process as a peripheral nerve disor-der. Autonomic neuropathy (and endothelial dysfunction) results in an impairment of vascular smooth muscle tone and consequently produces a vasodilatory condition in the small arteries of the distal extremities (20,21). Impairment of neurogenic vascular responses in patients with diabetic neuropathy has been supported by one study that consequently also showed preserved maximal hyperemic responses to skin heating in patients with Charcot arthropathy (22). In concert with associated arteriovenous shunting there is a demonstrable increase in bone blood flow in the neuropathic limb. The resultant osteolysis, demineralization, and weakening of bone can predispose to the development of neuro-osteoarthropathy (2,18-20,23,24). Several studies have demonstrated reduced bone mineral density with an apparent imbalance between the normally linked bone resorption and production in patients with osteoarthropathy (25-27). Specifically, greater osteoclastic than osteoblastic activity has been noted in acute neuroarthropathy, suggest-ing an explanation for the excessive bone resorption during the acute stage (20,25)." - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p. 271/272

[12] "Subsequently, Bailey and Root, in their 1947 series, noted that 1 in 1100 patients with diabetes mellitus developed neurogenic osteoarthropathy (7). In the classic 1972 Joslin Clinic review of 68,000 patients by Sinha et al. (8), 101 patients were encountered with diabetic Charcot feet. This ratio of 1 case in 680 patients with diabetes brought greater attention to this dis-order and characterized the affected patients’ clinical and radiographic presentations. In the subsequent 30 years, there has been a significant increase in the number of reports on diabetic osteoarthropathy, its complications, and management (6–10).The prevalence of this condition is highly variable, ranging from 0.15% of all patients with diabetes to as high as 29% in a population of only neuropathic diabetic subjects (2,8,10,11). Recently, a prospective study of a large group of diabetic patients from Texas reported an incidence of 8.5/1000 per year. Neuroarthropathy was significantly more common in Caucasians than in Mexican Americans. (11.7/1000 vs 6.4/1000) (12). Although this study may give us better insight into the true frequency of osteoarthropathy in diabetes, much of the data we currently rely on are based on retrospective studies of small single center cohorts. Nonetheless, the incidence of Charcot cases reported is very likely an underestimation because many cases go undetected, especially in the early states (2,11,13).The frequency of diagnosis of the diabetic Charcot foot appears to be increasing as a result of increased awareness of its signs and symptoms (14). Although the original descriptions of neuropathic osteoarthropathy were attributed to patients with tertiary syphilis, diabetes mellitus has now become the disease most often associated with this severe foot disorder. Not only are diabetic patients with Charcot foot deformities at greater risk of amputation than those with neuropathic ulcers without osteoarthropathy, a study from the United Kingdom has also found them to have a higher mortality (15)". - "The Diabetic Foot" (Second Edition), Aristidis Veves, John M. Giurini, Frank W. LoGerfo, Humana Press 2006, p.268/270

[13] ""The treatment of Charcot arthropathy is not yet well defined. Treatment had been limited to orthotic/molded shoe support, cast immobilization with varying periods of non-weightbearing and surgical débridement." - Musculoskeletal Disorders of the Lower Extremities, Lawrence M. Oloff, 1994 W.B.Saunders Co., p.206

[14] „Boala Charcot - Marie - Tooth! Cum sa vindeci boala in 2022?”. Boala Charcot - Marie - Tooth! Cum sa vindeci boala in 2022? ~ "Fii lumina acolo unde esti !". Accesat în 10 februarie 2022.

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