Charcot Neuropathy Flashcards
What is Charcot neuropathy?
Charcot neuroarthropathy (CN) is a progressive, deforming disease of the bone and joints, especially affecting the foot and ankle. However, it can affect other joints such as the wrist, knee, spine and shoulder.
What conditions can cause Charcot neuropathy?
- Diabetes
- Syphilis
- Chronic alcoholism
- Leprosy
- Syringomyelia
- Toxic exposure
- Poliomyelitis
- Spinal cord injury
- Rheumatoid arthritis
- Multiple sclerosis
- Congenital neuropathy
What is the prevalence of Charcot neuropathy as a complication of diabetes?
According to various authors, the prevalence of Charcot neuropathy as a complication of diabetes is 0.1% to 8%. However, the true prevalence is unknown because of a lack of population‐based studies as well as a consensus on diagnostic criteria.
What is the pathogenesis of Charcot Neuropathy?
The pathogenesis of CN is not completely understood. The neuro‐traumatic theory proposed by Volkman and Virchow in 1886 maintains that repetitive minor trauma to insensate joints leads to the fractures and disintegration of joints seen in CN. The neuro‐vascular theory maintains that autonomic dysfunction increases the blood supply to the limbs, leading to resorption of bones. Stevens and colleagues reported selective loss of small fibers for cold sensation in CN with preservation of those for perception of warmth and light touch. The role of pro‐inflammatory cytokines in the pathogenesis of CN has been widely researched. Receptor activator of nuclear factor‐κb ligand (RANKL) is expressed in response to activation by cytokines such as tumor necrosis factor‐α and interleukin‐1β. RANKL leads to maturation of osteoclasts by triggering production of nuclear factor‐κβ. In CN, uncontrolled production of these cytokines, RANKL and osteoclasts leads to local osteolysis13. Witzke and colleagues found fewer receptors for advanced glycosylation end‐products (RAGEs) in diabetic patients with CN. RAGE has been implicated in increasing activation of RANKL, which in turn leads to bone resorption through osteoclastogenesis as discussed earlier. In a recent study, Chantelau and colleagues found a high threshold for cutaneous pressure pain perception in Charcot feet. They further suggested that these patients fail to perceive inflammatory pain caused by trauma.
What is the most widely recognised classification system for Charcot Neuropathy?
The most widely recognized classification system for CN is the Eichenholtz system. He described three stages of progression of CN, namely fragmentation\dissolution, coalescence and reconstruction.
In stage 1 there is localized warmth, redness and swelling. X‐ray films show bony fragmentation, debris, fractures and subluxation/dislocation.
In stage 2 there is reduction of warmth and swelling clinically and absorption of bony debris, bony/joint fusion and sclerosis on X‐ray films.
In stage 3, there is absence of warmth, swelling and redness. X‐ray films in this stage show decreased sclerosis, osteophyte formation, joint arthrosis and deformity.
Shibata et al. modified this classification, adding a stage 0 in which there is localized warmth, redness and swelling but no visible abnormal radiological findings
What is the Sanders and Frykberg anatomical classification of Charcot Neuropathy?
Sanders and Frykberg described five patterns of joint destruction.
In Pattern I, metatarsophalangeal and interphalangeal joints are involved.
In Pattern II - Lisfranc’s joint (tarsometatarsal)
In Pattern III - Chopart’s (talonavicular, calcaneocuboid) and naviculocuneiform joints.
In Pattern IV - ankle and subtalar joints.
In Pattern V - the calcaneum.
According to this classification, Patterns II and III are associated with the greatest complication rates.
What are the anatomical classification systems for Charcot Neuropathy by Brodsky? What about the classification system by Rogers and Bevilacqua?
Brodsky described four types of disease pattern based on frequency of joints affected, the commonest involvement being of the tarsometatarsal joint. Type 1 includes Lisfranc’s joint (tarsometatarsal); Type 2 Chopart’s joint and/or the subtalar joint; Type 3A the ankle joint (Type 3B the calcaneum).
Rogers and Bevilacqua proposed a classification system based on location of foot involvement and associated complications. They also postulated a high risk of amputation with hindfoot/ankle involvement as well as in the presence of osteomyelitis in CN.
How does Charcot Neuropathy typically present?
Patients usually present with redness, swelling and pain. Although any part of the foot and ankle may be involved, the mid‐foot is most frequently affected. Although the affected limb is insensate, pain and swelling are the usual complaints by patients seeking medical consultation. The vascularity of the limb is usually preserved and the peripheral pulses may be bounding. However, swelling or oedema may make their palpation difficult. Radiographs of the foot often reveal bony erosion, fracture and subluxation or dislocation of multiple joints. Over time, the redness and warmth decrease and deformities develop.
Radiologically, the bones show osteosclerotic features and the fractures unite. A typical deformity associated with this condition is the rocker‐bottom foot, which is caused by collapse of the longitudinal arch of the foot. This, along with instability of the ankle joint, is reportedly the major cause of morbidity in CN. It leads to a high pressure area at the base of the foot which in turn predisposes to ulceration and subsequent infection.
What is the biggest differential diagnosis of acute Charcot Neuropathy?
The most problematic differential diagnosis of acute CN is osteomyelitis. Osteomyelitis and CN are not mutually exclusive and can occur simultaneously. To add to the confusion is the lack of inflammatory response seen in diabetic patients because of immunopathy. Any associated ulcer should be thoroughly probed. Osteomyelitis usually spreads through a contiguous break in the skin. Presence of an ulcer tilts the diagnosis in favor of osteomyelitis.
What are some neurological and temperature findings on examination in patient with Charcot Neuropathy?
NEUROLOGICAL TESTING:
A variety of neuropathies are associated with diabetes. These include sensorimotor neuropathy, distal symmetric polyneuropathy, diabetic mononeuropathy, focal neuropathy, mononeuritis multiplex, diabetic amyotrophy and diabetic autonomic neuropathy. Unger and Cole stated that “Peripheral neuropathy is the most common type of neuropathy seen in clinical practice, and causes either pain or loss of feeling in the toes, feet, legs, hands, and arms”. It is necessary to examine for loss of pressure and vibration sense using Semmes‐Weinstein monofilament and a 128 hz tuning fork, respectively. Autonomic neuropathy is diagnosed clinically by measuring heart rate variability (HRV) with deep breathing or orthostatic blood pressure. Decrease or absence of HRV is the most consistent and earliest indicator of autonomic neuropathy in the diabetic patient.
TEMPERATURE OF THE FOOT
In the acute stage of CN, the foot is warm. A temperature difference between the feet of 2 °C is considered significant. This can be measured using an infrared thermometer. Furthermore a temperature difference of <2 °C between the limbs is used as a determinant of the end of the acute phase. One study found no relapse when a foot skin temperature difference of <2 °C was used as a clinical marker for immobilization withdrawal. In a recent study, Najafi et al. used a thermal imager to study variability of plantar thermal response caused by walking in Charcot and non‐Charcot feet. They found that after 50 steps there was a significant increase in the plantar temperature in CN patients. However in the later stages of CN, this temperature differential may not be found.
What are the ‘Five D’s’ which summarise the XR findings (foot and ankle) of Charcot Neuropathy?
Plain weight‐bearing X‐ray films of the foot and ankle are a readily available and relatively cheap mode of investigation. However, they are not of much help during the acute phase (“stage 0” as described by Shibata and colleagues).
Rajbhandari et al. summarized the findings on X‐ray films as “The five D’s: joint distension, dislocation, debris, disorganisation and increased density”.
According to the Eichenholtz classification, which is based on radiographic changes, stage 1 shows fragmentation of bone, bony proliferation and joint destruction/dislocation; Stage 2 resorption of bone debris, fusion of bony fragments and sclerosis of ends of bone; and Stage 3 sclerosis decreases and joint arthrosis and osteophytes become evident
What
Aside from XR, what are other imaging modalities for Charcot Neuropathy?
CT, MRI and PET Scan
Computerized tomography is more valuable for surgical reconstruction and preoperative planning than for diagnosing CN. CT is useful in the early stages of spinal neuroarthropathy; however, the role of CT in diagnosis of the Charcot foot is still not validated.
Magnetic resonance imaging is becoming a popular investigation for a variety of foot problems. In chronic CN, MRI shows low signal intensity in subchondral bone on both T1 and T2 weighted images; this correlates with sclerosis on radiographs. In contrast, in osteomyelitis there is low signal intensity on T1‐weighted and high signal intensity on T2‐weighted images. However, differentiating acute Charcot foot from osteomyelitis remains a challenge. The very similar clinical presentation of these two entities causes confusion in the diagnosis and overlap of the MRI findings adds to this confusion. However, there are some clues that can help to clinch the diagnosis.
On MRI, a Charcot foot will show localized juxta‐articular edema, whereas in osteomyelitis the edema is more on one side of the joint and is not confined to the juxta‐articular area. Clinically, osteomyelitis affects a single bone in the forefoot or hindfoot, whereas CN affects many bones, commonly in the midfoot. In their study of MRI findings and clinical symptoms in the early stage of CN, Schlossbauer et al found a strong correlation between MRI findings and clinical assessment. They also proposed using MRI to monitor pressure relieving treatment.
Positron emission tomography (PET) has been recently advocated for differentiating between early stage CN and osteomyelitis. PET has a distinct advantage over MRI in patients with metal implants. Addition of fluorodeoxyglucose (FDG) further adds to the diagnostic capability of PET. FDG enters the cells and is phosphorylated by hexokinase into fluorodeoxyglucose‐6‐phosphate, which cannot be metabolized further. Hence it starts accumulating inside activated white blood cells at the site of infection and inflammation. There is some controversy regarding FDG uptake in the presence of hyperglycemia in diabetes. Keidar et al. found no relationship between abnormal FDG uptake and glycemia. Zhuang et al. found PET–FDG to be 100% sensitive and 87.5% specific for excluding chronic osteomyelitis. Basu et al. found FDG–PET to have high negative predictive value in ruling out infection in diabetic patients with foot ulcers. Höpfner et al. recommended PET over radiography and MRI for preoperative evaluation of CN patients. Addition of CT/MRI to the scintigraphic images of PET (hybrid PET) further enhances the specificity of PET. However, the high cost and limited availability may limit its use.
What is the first-line treatment for Charcot Foot / Ankle?
EARLY OFFLOADING WITH A TOTAL CONTACT CAST (TCC)
- the TCC assists even distribution of forces across the plantar surface of the foot, preventing further destruction of involved bones and joints and eventually limiting the degree of deformity. Generally, non-weight-bearing with a TCC is continued until swelling and hyperemia have resolved and foot skin temperature differences have decreased. A TCC is usually continued for 8-12 weeks. To avoid cast complications, frequent cast changing is recommended. However, Clohisy and Thompson highlighted the risk of fracture due to increased stress on the contralateral weight‐bearing limb. The location of the arthropathy also determines how long the TCC is indicated. Sinacore stated that, when a TCC is used, forefoot arthropathy heals faster than that of ankle, midfoot and hindfoot. After the acute stage has subsided, the patient is advised to wear an ankle‐foot orthosis or a custom‐made shoe. Traditionally Charcot Restraint Orthotic Walkers have been used at this stage. Again, their application requires expertise. With any form of offloading further support in the form of crutches and wheelchair are also advocated.
Are there any pharmacological therapies that have been tried in Charcot Neuropathy?
Pharmacological therapy is not yet of proven efficacy; further studies are required to determine its role.
Although bisphosphonates have shown some promise in the acute stage of CN, the evidence for them is inconclusive. They act by inhibiting osteoclast‐mediated bone resorption. Their antiresorptive effect on bone is mediated by inhibition of hydroxyapatite breakdown and osteoclast apoptosis. Pamidronate (oral and intravenous), alendronate and zolendronic acid have been assessed in some randomized control studies (RCT). One study found intranasal calcitonin to be effective in arresting excessive bone turnover in patients with acute CN. Further larger clinical trials are required to establish the benefits of the pharmacological agents recommended for CN.
What type of surgery is done for patients with Charcot Neuropathy? When is this typicallly done?
ack of randomized control studies (due to the rarity of the disease) and the diversity of joints affected by this disease preclude recommendation of any one specific surgical technique75. Surgery is usually reserved for patients in whom conservative treatment has failed or for treating complications like deformity, joint instability, infection and recurrent ulceration. The sequels of CN increase the morbidity and mortality of affected patients. The aim of surgery is to stabilize and align the foot/ankle and make it amenable to wearing appropriate braces or footwear. The procedures used for treatment of Charcot feet are realignment and arthrodesis, exostectomies and amputation. For managing associated ulcers and infection, debridement is performed with or without the use of antibiotics. Some centers advocate early surgical intervention to avoid the potential high cost of, and complications associated with, prolonged immobilization
