CHAPTER 42 NEUROPATHIC SECONDARY TO CONGENITAL INSENSITTVITY TO PAIN WITH ANH]'DROSIS

Robert M, Goecker, D.P.M.

Neuropathic arthropathy of the foot and ankle has been linked to several different disease processes such as mellitus, tabes dorsalis, , etc. A very rare cause of neuropathic arthropathy is a group of diseases classified as congenital indifference to pain.1 This group includes congenital insensitivity to pain and hereditary sensory neuropathies Type I - IV. Congenital rrsensitivity to pain with anhydrosis (CIPA) makes up an even smaller percentage of patients clas- sified with hereditary sensory neuropathy. Episodes of feveq lack of perspiration, absence of pain, self-injury, painless fractures and mental retardation characterize CIPA. Usually it is recognized early in infancy, because of high fevers secondary to the lack of perspration. Figure 1A. The severe valgus deformity of the ankle with instability The primary clinical feature of CIPA is congenital anal- lead to pressure ulcers over the dislocated malleoli. gesia, with no response to painful stimuli, which can lead to self-mutilation, multiple orthopedic fractures and sometimes Charcot .'11

CASE STUDY

An B-year-old female patient was seen after referral with chronic ulcerations over her right medial malle- olus and a complex history of possible neuropathic afihropathy, chronic and apparent recurrent right ankle infections with swelling, red- ness and fevers, The patient had increasing valgus deformity of the ankle with instability, exceeding the capaci|y of a patellar tendon brace especially over the dislocated medial malleolar region. The defor- mity led to the pressure ulcerations. Musculoskeletal examination revealed a normal left foot and ankle for the patient's age. Her right foot and ankle on the other hand was grossly deformed with a significant amount of heterotopic bone formation. The ankle was extremely unstable with significant crepitation. Similarly the Figure I B. Anterior vicq ol Ihe se\ cre deiormiry. subtalar joint had excessive completely non- anatomic motion. In stance the patient's calcaneus was almost completely laterally dislocated from underneath the tibia.(Fig. 1) The neurological CHAPTER 42 215 examination revealed normal deep tendon reflexes bilaterally. The patient did not respond to painful stimuli and had no ability to differentiate sharp and dull sensations. However, the patient was hyperes- thetic to light touch and vibration sensation was normal. Muscle strength was normal and rated at 5/5 for all lower exremity groups. Radiographic evalua- tion revealed complete destruction of the right ankle joint. There was complete avascular necrosis and disintegration of the talus with a significant amount of heterotopic bone formation. (Fig. 2) There was no evidence of a focal lyic area (Brodie's abscess) or periostitis. The destruction was so severe that the distal tibial and fibular physbal regions appeared Figure 2A. Radiographic evaluation revealed complete destruction of involved in the destmctive process as well. the right ankle joint. There was complete avascular necrosis and dis- A detailed history revealed problems with integration of the talus with a significant amount of heterotopic bone formation. fevers of unknown origin as an infant which went undiagnosed until the patient was three-years-o1d. At that time, her pediatrician diagnosed her with anhydrosis. Over the next several months, an even- tual diagnosis of congenital insensitivity to pain with anhydrosis was made. At that time she had experienced no orthopedic problems. However, at age 5 she had an infection from a sore on her right hallux that developed osteomyelitis and eventually required a partial hallux . During her postoperative convalescence she developed a pres- sure sore from a bandage (cast). At the same time her ankle became red, hot and swollen. Aspirations of the ankle were all negative, however, cultures of the soft tissue pressure wound yielded Staph aureus and pseudomonas. A bone scan (Tcppmdp) Figure 28. AP view was performed and a presumptive diagnosis of osteomyelitis was made. Intravenous antibiotics were then utilized for several months with no decreasing function and consideration of amputa- improvement noted. Serial radiographs taken dur- tion lead to an eventual referral to the author's ing this time revealed progressive talar destruction, office for surgical consultation. which was considered an avascular necrosis or a After the initial visit, a period of prolonged septic process. At this time the patient had an inci- immobilization and external bone stimulation was sion and drainage, however, all cultures were recommended in an attempt to gain more stability, negative. The open wound eventually healed with and avoid the need for surgery. After a period of decreased activity and bracing, and the acute approximately 3 months, no significant improve- also subsided. At this time neuro- ment in the right ankle was noted. During this time, pathic osteoafihropathy was considered as part of the patient dislocated her contralateral hip on two the cause of the ankle deterioration. However, different occasions without a severe traumatic his- chronic osteomyelitis at this stage was also possible tory. In both situations, the hip was reduced due to multiple deep ulcerations and open wounds without the need for surgery. During the recovery which could have caused a contiguous spread period of the second left hip dislocation it was osteomyelitis. During the next two years increasing decided to proceed with right ankle surgery. It was ankle deformity was noted, low-grade inflamma- felt that the altered mechanics of the right ankle tion continued to be present, and neurotrophic was probably affecting the other lower extremity ulcerations began to develop. Increasing deformity, joints. The ankle was so non-functional at the time, 216 CHAPTER 42

Figure JA. Postoperative radiographic appear- Figure 38. AP vieu' of the ankle/leg ance of the tibiocalcaneal arthrodesis with Ilizarov frame.

Figure 3C. Lateral vien of the foot Figure 4. Postoperative clinical appearance of the tibiocalcancal ar1l'rodesis u,-ith Ilizarov frame. amputation had already been recommended by The patient successfully underwent tibio- other physicians. calcaneal arthrodesis with implantation of an A tibiocalc^fieal arthrodesis with an Ilizarov internal bone stimulator and application of an frame was recommended. Other fixation modalities Ilizarov frame. (Figs. 3, 4) Intraoperative bone were considered but, since the patient had signifi- biopsy reveaied marked degenerative joint disease cant problems with pressure sores and compliance consistent with neurotrophic arthropathy with no with non-weightbearing casts, external fixation was evidence of osteomyelitis. However, intra-operative deemed the most appropriate. Use of an llizaroy bone culture was positive for Staph aureus. Since frame would also avoid crossing the growth plates the culture and biopsy provided conflicting results with internal fixation. No further work-up regard- a long-term course of chronic antibiotic suppres- ing the patient's possible osteomyelitis was sion therapy was instituted. The patient was kept performed prior to surgery, however intra-opera- non-weightbearing during the initial postoperative tive cultures and bone biopsy were planned. period because the left hip was still healing from its CHAPTER 42 217 second dislocation. At sk weeks postoperatively hypermobile and had fragmented the wire in the the patient fractured her tibia just above the supe- region of the sinus tarsi and navicular, anterior to rior ring of the llizarov frame likely from a stress the tibiocalcaneal arthrodesis site.(Fig. 6) Another riser that developed from the patient crawling on Charcot event was suspected, but with the history her hands and knees. Closed reduction with exter- of the previous osteomyelitis and the previous pos- nal fixation was performed, bridging this fracture itive bone culture, the internal bone stimulator was with another ring superiorly. Shortly after this frac- removed and an I&D was performed. Infectious ture, the patient began full weightbearing with the disease stafied intravenous antibiotics. AII cultures Ilizarcv frame. During the postoperative convales- were negative except for one which grew a coagu- cence, several postoperative pin tract infections lase negative staph. The patient healed quickly and were encountered and appropriately treated. the swelling and redness improved. Approximately four months status post tibio- During her immobilization on the right leg she calcaneal arthrodesis, and just over two months suffered a midshaft tibia fracture from a simple hop after closed reduction and external fixation of the on her left leg. Two months later while still non- tibial fracture the l\izarov frame was removed. The weightbearing because of her left tibial fracture, tibial fracture healed uneventfully without malu- localized redness, increased temperature and nion. The tibiocalcaneal arthrodesis did not entirely swelling over the lateral aspect of her right ankle consolidate, but was stable. (Figs. 5-7) The stability reoccurred in the region of old pin sites. A local of the ankle was confirmed with live C-arm fluo- I&D was performed by another surgeon in the roscopy. Ambulation with a custom-made shoe author's absence, which grew Staph aureus. with a :1/t inch lift correcting for the leg length dis- Infectious disease and others recommended a crepancy and a MPJ rocker was ordered. below-the-knee-amputation with the patient Approximately two weeks after ambulation with becoming neutropenic from IV antibiotics. Their the custom-made shoe was begun, swelling and feeling was that it was a primary infectious process redness developed once again. Radiographic eval- (chronic osteomyelitis and a septic joint). uation revealed fragmentation of the internal bone Considering the very confusing history with stimulator wire. This was clearly caused by motion. conflicting bone culture and bone biopsy results The midtarsal joint (navicular) was extremely and bouts of recurrent inflammatory processes) a T-99 coupled with an I-777 bone scan was ordered with a 24 hour delayed reading. The hospital sub- stituted a T-99 HMAPO scan which showed no focal activity in the right ankle in the delayed images. In the T-99 bone scan only the left healing tibial fracture showed an increase in uptake com- pared to the contralateral extremity.

Figure 5. Postoperative radiographic appearance of the tibiocalcaneal arthrodesis and tibial frac- ture after Ilizarov frame removal (oblique Figure 6. Postoperative radiographic appearance of tibiocalcaneal ankle/leg view). The bone callous bridging the arthrodesis after lhzar ov frame removal (lateral view). Note the frag- tibial fracture is clearly seen. mentation of the internal stimulator wire in the region of the navicular. 218 CHAPTER 42

Figure 7. Postoperative clinical appearance of Figure 8. A custom macle shoe with a 3/. inch lift tibiocalcaneal afihrodesls 2 weeks after Ilizarov coffecting for the leg length discrepancy and a frame removal. MPJ rocker was ordered for ambulation as well as a patellar tendon brace.

The patient was taken off all IV antibiotics due however, the pathophysiology has been linked to to her neutropenia. Once again the inflammation abnormalities in the peripheral sensory nerves. eventually resolved and her wound healed conselv- Several authors have reviewed peripheral nerve atively without antibiotics. The patient was placed biopsies under electron microscopy.3 6 Goebel et al. back into a pateTlar tendon brace for ambulation, examined sural nelve biopsies and observed an which has worked well over the last four months. almost complete absence of unmyelinated fibers (Fig. B) The tibiocalcaneal arthrodesis remains a sta- and a slight decrease in small myelinated fibers.6 ble pseudoafihrosis with no varus or valgus motion. Rafel et al. also showed similar findings.{ Itoh et al. Dorsiflexion is present, but this occurs in the mid- noted extreme paucity of unmyelinated fibers and tarsal joint. There has been no further skin a reduction in myelinated fibers, especially small breakdown or ulceration in the right foot, ankle or fibers. They also repofted that the endoneurium leg. The patient is currently ambulating in her patel- consisted of abundant collagen fibers.t In summary, lar tendon brace and adjusted shoe with no biopsies of peripheral nerwes in patients with this complaints or difficulty and has significantly condition have shown a severe decrease in the increased her activity. However, the patient and her number of smail (A-delta) myelinated fibers and a family know that further orlhopedic problems are marked decrease in the number of unmyelinated likely to occur in the future. The family has declined (type C) fibers. These fibers are yery important the recommendation for household ambulating component for the sensation of pain.36^ Swanson et only, with use of a wheelchair for other activity. al. showed that there was an absence of small neu- rons in the dorsal ganglia, a lack of smal1 fibers in DISCUSSION the dorsal roots and the absence of Lissauer's tract in a necropsy of a twelve-year-old who died sec- This case is a typical example of congenital insen- ondary to a febrile illness. Therefore, he suggested sitivity to pain with anhydrosis. Dearborn first that this condition could be secondary to a migra- described congenital insensitivity to pain in 7932.' tion defect in the neuron precursors and an The syndrome with anhydrosis was classified by interruption in maturation.T Dyck and Ohta as type IV hereditary sensory neu- Goebel et al reported on two patients who ropathy.3 The cause of this disorder is unknown, died at an earTy age secondary to not being able to CHAPTER 42 219

control body temperature in the presence of severe When considering surgery on patients who infection.6 Unfofiunately, the patient in this case suffer from CIPA, one must consider the impor- study lost an older sister to such a circumstance at tance of the management of body temperature. just over a yeat old. Skin biopsy results in patients Typically, only light anesthesia is necessary due to with this condition have shown normal sweat the lack of pain perception. Also positioning and glands with no unmyelinated nerwe fibers around maneuvering are extremely important to avoid joint the sweat glands leading to the anhydrosis and extension and further injury.'o decreased abiliry to thermoregulate.3 The lack of sensation (indifference to pain) SUMMARY causes the inability to perceive or prevent trauma, or to avoid ovelarse injuries, which leads to the Neuropathic afihropathy of the foot and ankle is a increased risk of multiple orthopedic complications well-recognized condition in diabetes mellitus and and possibly Charcot joints. The pathogenesis of other more corunon forms of neuropathy. This case this type of arthropathy is the same as that in other study reviews another possible cause of neuropathic causes of Charcot joints.s A loss in pain sensation osteoafihropathy. Congenital insensitivity to pain and/or proprioception leads to abnormal relaxation with anhydrosis (CIPA) is characterized by episodes of supporting periarticular structures. This laxity of fever, lack of perspiration, absence of pain, self- results in joint instability and continuous micro- injury, painless fractures (multiple orthopedic trauma. Eventually chronic inflammation causes complications including Charcot joints) and mental joint degeneration, incongruity, fracture and neuro- retardation. The case reported showed the impor- pathic changes from continued weightbearing tance of a proper initial diagnosis and management forces. Eventually, x-rays reveal marked osteope- of neuropathic arthropathy in avoiding the potential nia, sclerosis, fragmentation, large osteophyes and morbidity associated with Charcot joints. ioint sublLrxation. In retrospect, the case presented began as an acute tibiotalar Charcot joint that was not properly REFERENCES immobilized and eventually became infected from 1. MacEwen GD, Floyd GCr Congenital insensitivity to pain and its a contiguous spread osteomyelitis from deep neu- orthopedic implications. Clin orthap 6g,lOO, f970. rotrophic ulcerations rather than from a 2. Ozbarlas N, Sarikayalar F, Kale G: Congenital insensitivity to pxin with anhydrosis. Catis 51: 373-374,1993. hematologic osteomyelitis or a septic joint. It is 3. Okuno T, Inoue A,Izumo S: Congenital insensitivity to pain with clearly evident in the literature that these patients anhydrosis../ BaneJoint Surg 72A: 279-282, 1990. have an extremely high incidence of fracture/dislo- 4. Rafel E, Alberca R, Bautista J, Navarete M, L^zo J: Congenital insensitivrty to pain with anhidrosis. Afucle Nerue 3: 276-220, 7980. cations especially in the tibia and femur causing the 5. Itoh Y, Yagishita S, Nakajima S, Nakano T: Congenital insensitiv- vast majority of these patients to become wheel- ity to pain with anhidrosis: morphological and morphometrical studies on the skin and peripheral nerves. Neara?etliatrir 17:703- chair bound.3! Theodorou et al. reported tlvo cases 110,1986, of CIPA which resulted in neuropathic arthropathy, 6. Goebel HH, Veit S, Dyck PJ; Confirmation of virtual unmyelinated fiber absence in hereditary sensory neuropathy type IY. Neuropathol bllateral Charcot ankle joints and in the other case Exler Neurol 39:670-675, 7980. affected a foot.e Other reported orthopedic compli- 7. Swanson AG, Buchan GC, Alvord EC Jr; Anatomic changes in con- gefltal insensitivity to pain. Absence of small primary sensory cations have included spinal instability and lumbar neurons in ganglia, rools and Lissauer's l;lact. Arch Neuro 1,2:712, 7965. neuropathic arthropathy.8 have been 8. Piazza MR, Basset GS, Bunnel WP: Neuropathic spinal arthropa- thy in congenital insensitivity to pain. Clin Orthop Rel Ru 236: necessary patients CIPA mu1- for some with due to 775-179, 1988. tiple fractures, instability, malunion, infections and 9. Theodorou SD, Rasheed A, Makhlouf SA, et a1.: orthopedic com- gangfene.10,11 plications in congenital sensory neuropathy with anhydrosis (congenital absence to pain). Axa )rtbop Belg 51:91-702, L985. 10, Mitaka C, Tsunoda Y, Hikawa Y, Sakahira K, Matsumoto I: Anesthetic manaElement of congenital insensitivity to pain with anhydrosis, Anest be.r kt logy 63 : 328-329, 1985. 11. Layman PR: Anesthesia for congenital analgesia. A case repofi. Anestbesia 11:395-31)7. 1985.