Abstract
BACKGROUND
Charcot-Marie-Tooth (CMT) disease is, in reality, not a single disease, but a group of inheritable defects in the proteins of the peripheral nerve myelin sheath. 6 The disorder was first described in 1886 by the French neurologist Jean Martin Charcot and his pupil Marie 5 as well as independently by Tooth in England. 28 Much like the neuroarthropathy that also bears his name, Charcot's description of the disease was exhaustive, but his explanation of the pathophysiology was incorrect; he attributed it to a myelopathy. Although Tooth 28 described the disease slightly later, he accurately classified it as a peripheral nerve disorder.
The nomenclature associated with CMT over the years has been particularly confusing and significantly limits the value of the historical literature on its orthopaedic management. Peroneal muscular atrophy (PMA) was once used as a general term to describe pattern of motor wasting, and the abbreviation appears in the literature even today. Before the current understanding of the genetic underpinnings of the disease, Dyck and Lambert developed an extensive classification of inheritable motor neuropathies based on their electrodiagnostic characteristics. 7 They coined the classification of hereditary motor sensory neuropathies I—VII (HMSN I-VII).
The purpose of this review was to discuss the modern basis for classifying this complex disorder and to review the basis for treatment of its most symptomatic feature: the progressive cavus foot deformity.
THE MODERN GENETIC CLASSIFICATIONS
Today, CMT disease is understood in genetic terms, and a large variety of specific genetic defects have been identified with the disease. 6,21 Specific tests exist for many of the identified phenotypes if genetic counseling is desired, but there is currently no intervention guided by knowledge of any patient's specific subtype. All of the forms of CMT are inheritable, but roughly half of all cases of CMT represent new mutations or recombination errors. A negative family history cannot, therefore, exclude the possibility of the disease. The major subtypes of CMT are described in Table 2.
CMT-1A is by far the most common form of the disease. Its genetics are unique and deserve special attention. The pathology is produced by a problem in the gene for peripheral myelin protein-22 (PMP-22), a constituent protein of myelin whose function is poorly understood. While point mutations of PMP-22 can produce the CMT-1A phenotype, it is most commonly associated with a gene dosage effect. A recombination error results in a segmental trisomy along a small segment of chromosome 17; there are three copies of an otherwise normal PMP-22 gene in this location. The precise function of PMP-22 is unknown, but it is a critical myelin constituent. A relatively precise amount of the protein product is required for normal myelin function. 19 Therefore, instead of a mutation rendering the protein ineffective, this is an example of a gene dosage effect.
Level of evidence and grades of recommendation
PMP-22 is involved in another closely-related inheritable disease, hereditary neuropathy with liability to pressure palsy (HNPP). 13,17 This disorder is much rarer than CMT-1A and is characterized by episodic but severe compression nerve palsies and has been described in several family groups since its original description in a family of potato-diggers who developed peroneal motor palsies associated with constant stooping and knee flexion. This disorder also involves a normal gene for PMP-22, but instead of a focal trisomy, one copy of the gene is missing. It is, therefore, a gene dosage effect in the opposite direction from CMT-1A.
LOWER EXTREMITY MOTOR WEAKNESS IN CMT
The nerve dysfunction in CMT takes a variable time course, but it also is inexorable and progressive. In patients with CMT-1, electrical evidence of nerve dysfunction often is present by 2 years of age, although clinically evident weakness may not be apparent for many years. 2 The symmetric reduction of lower limb reflexes was defined by Berciano et al. 3 as a constant feature even before symptoms. Given that half of the cases are new genetic events, it is not uncommon for even a relatively athletic teenager to present as a new case of CMT with bilateral cavovarus feet and unstable ankles.
Unlike classic symmetric polyneuropathies, which present with nerve dysfunction always directly proportional to the length of the affected peripheral nerve, the hallmark of CMT is the selective loss of the anterior compartment muscles of the leg. The lateral compartment is severely affected as well, but careful examination will reveal that the peroneus brevis muscle is affected much more severely than the peroneus longus muscle. This was first described clinically by Mann and Missirian 16 and was subsequently confirmed with MRI by Tynan et al., 29 who found an absence of atrophy of the peroneus longus muscle belly even while function of the adjacent anterior tibial and peroneus brevis muscles is lost.
Subtypes of Charcot-Marie-Tooth Disease
Another inconstant but puzzling feature of CMT is the occasional extensor hallucis longus (EHL) sparing, despite its location more distal in the anterior compartment than the anterior tibial muscle.
The posterior compartment of the leg usually is spared until quite late in the course of the disease. More distally, the motor supply to the foot intrinsics is lost early, resulting in clawtoes, which often are the first noticeable signs of pathology. The continued pull of the foot extrinsics also begins the early formation of the cavus foot. Recent MRI findings in early-stage CMT patients by Gallardo et al. 9 indicate that a moderate cavus foot can develop purely from loss of the intrinsics combined with continued functioning of the peroneus longus.
These unusual features of the motor weakness patterns in CMT, particularly the selective sparing of the peroneus longus and occasionally the EHL, have led to speculation about a possible subtle role for compression neuropathy in the development of nerve dysfunction. The close genetic association of CMT to hereditary neuropathy with liability to pressure palsies (HNPP) suggests this may be the case. Additionally, the more severely affected anterior and lateral compartments rely on the vulnerable peroneal nerve branches crossing the fibular neck for their innervation. The usually severely affected anterior tibial muscle is supplied by a branch that courses over the periosteum of the fibular neck, while branches to the relatively spared peroneus longus often originate proximal to the fibular neck. 10
FOOT DEFORMITIES IN CMT
Regardless of the reason for the unusual patterns of motor weakness in CMT, once those patterns are in place, the foot deformities that result from them can readily be understood. In each, the deformity is the result of an imbalance between an agonist and antagonist muscle: 1,11,12,16,23
Clawtoes result from the loss of the foot intrinsics with the relative sparing of the extrinsics to the toes. Balance in the toes, just as in the fingers, results from the modifying force of the intrinsic musculature to flex the metatarsophalangeal (MP) joint and extend the interphalangeal (IP) joints. When function of the intrinsics is lost, the unopposed force of the extrinsic musculature dorsiflexes the MP joints and flexes the IP joints, resulting in a clawtoe deformity.
Forefoot cavus results primarily from the action of the spared peroneus longus on the first ray, which serves to plantarflex the first metatarsal and overpower the affected anterior tibial muscle. The plantarflexed first ray increases the height of the arch and secondarily causes the subtalar joint to tilt into varus. Additionally, the arch is raised through the windlass mechanism which tightens the plantar fascia as the MP extension contractures develop as part of the clawtoe deformity. The term forefoot cavus is used to imply that the cavovarus foot results from the plantarflexion of the first ray. Radiographically, this means that the usual direct line that can be drawn down the talus and first metatarsal on a standing lateral view of the foot demonstrates plantarflexion at the base of the first ray. This can be distinguished from hindfoot cavus, in which an excessive calcaneal pitch angle is the primary cause of the deformity. Hindfoot cavus usually is seen today in idiopathic cavus foot deformity, but was historically common in patients with poliomyelitis who had isolated paralysis of the gastrocsoleus muscle.
Hindfoot varus in CMT results from both a direct mechanism and an indirect mechanism. Hindfoot varus is produced indirectly because the peroneus longus remains strong while the anterior tibial muscle weakens, leading to plantarflexion of the first ray. The resulting forefoot position leads to a compensatory hindfoot varus position as the hindfoot inverts through the subtalar joint, which remains supple at least in the early phases of the disease. Inversion of the hindfoot is produced directly by the posterior tibial muscle, which usually is spared long after the peroneus brevis is affected. The resulting hindfoot varus predisposes the patient to recurrent inversion injuries of the ankle, particularly when the active stabilizing force of the peroneus brevis is diminished.
Foot drop results simply from the failure of the anterior tibial muscle while the gastrocsoleus and deep posterior compartment are spared. Like inversion instability of the ankle, this usually is one of the most symptomatic features of the disease.
Clawed hallux represents a special case. In patients with sparing of the EHL, a very severe clawtoe deformity develops with a dramatic extension posture at the MTP joint. In this situation, the EHL is being used in this situation as an accessory dorsiflexor of the ankle to supplant the weakened anterior tibial muscle.
EVALUATION
The first step in the examination of a patient with bilateral cavus feet is to establish the diagnosis. CMT is the most common neurologic cause of cavus foot deformity encountered in the typical foot and ankle practice, but many adult patients with cavus feet have no clear etiology for the deformity. 4 The percentage of new diagnoses in a pediatric population can be remarkably high, estimated at 78% of patients with bilateral cavus feet in a recent retrospective review by Nagai et al. 18 (Level IV evidence). Nevertheless, the list of other neurologic causes of a cavus foot is lengthy and contains several potentially dangerous conditions (Table 3). Dramatic hyperreflexia or any significant asymmetry in reflexes or motor patterns is suggestive of a spinal cord lesion and mandates an MRI and neurologic consultation. CMT is a purely peripheral nerve disorder; it is not associated with spasticity.
GUYTON
Other potential neurologic causes of the cavus foot
Although 50% of cases represent a new deformity, a thorough family history is warranted. A history of recurrent ankle sprain is most common, but some patients only recall a parent with awkward foot posture. A history of a close relative becoming wheelchair bound or developing respiratory limitation may be a clue to a more aggressive variant of the condition.
In a patient with suspected CMT, an examination of the hands also is warranted. The upper extremity manifestations of CMT cause some degree of dysfunction, although rarely to the extent of the foot deformities. Nevertheless, denervation and atrophy of the hand intrinsics are useful signs to confirm the presence of a systemic neuropathy. The thenar and hypothenar eminences are symmetrically atrophied, and abduction of the digits is impaired. Subtle involvement can be best identified by palpating the first dorsal interosseus muscle along the radial border of the second metacarpal while abducting the index finger in the neutral plane of the palm. The digits abduct with activation of the long extensors, and if their function is not eliminated in this way they can be used to substitute for the dysfunctional intrinsics.
History-Taking
A history of lateral ankle instability is common and should be carefully elicited. Patients may not have classic ankle sprains but may instead have a sense of unsteadiness or imbalance on the foot. The history of the patient's bracewear may help avoid duplication of previous efforts. Fatigability, usually manifested as the development of a dropfoot and steppage gait by the end of the day, is a common early sign of decompensation. Finally, determining whether or not a patient is willing to accept a simple brace as a potentially unavoidable outcome despite surgery is important in avoiding disappointment later.
The CMT-Specific Physical Examination
With the diagnosis of CMT established, the physical examination should answer three questions that affect treatment:
Which motor units remain functional?
How flexible or rigid are the established deformities?
Is ligamentous laxity present?
The motor examination should focus on the relative balance of the agonist-antagonist pairs that generate the foot deformities. Active dorsiflexion against resistance can evaluate the anterior tibial muscle and help detect the use of the EHL as an accessory dorsiflexor, resulting in a clawtoe deformity of the hallux. Resisted eversion of the foot directly tests the peroneus brevis, while the longus can be partially isolated by asking the patient to depress the first ray.
The rigidity of the deformities determines to what degree tendon transfers or bony correction or fusion can be used for correction, as well as, the likelihood of a successful correction with bracewear. Clawtoes often are the first manifestation of CMT and are commonly rigid by the time patients seek medical advice. The forefoot deformity often is rigid as well, with a fixed plantarflexion of the first ray. The hindfoot varus that it produces may remain supple for many years. This can be determined by evaluation of the subtalar joint or by the Coleman block test. In the latter, the patient stands with the lateral border of the foot on a block approximately 0.5-inch to 1-inch high, allowing the medial side of the foot to rest unsupported. If the calcaneus, viewed from behind, successfully tilts out of varus and into valgus with this maneuver, the hindfoot usually is supple enough that forefoot correction alone will be sufficient. 20
Ligamentous laxity often is the presenting complaint for CMT patients, particularly those who represent new diagnoses. The varus alignment of the hindfoot leads to a lifetime of progressively severe inversion injuries, and the ankle demonstrates mechanical laxity in the anterior talofibular (ATFL) and calcaneofibular (CFL).
Imaging Studies
Radiographs of patients with CMT primarily serve to validate the deformities seen on clinical examination and ensure the absence of arthrosis. Hindfoot varus is seen on the lateral standing radiograph as a “look through” sign in the posterior facet of the subtalar joint; there is no overlap of the lateral process of the calcaneus. A line drawn down the talar neck on the lateral radiograph is ordinarily collinear with one down the center of the first metatarsal. This talo-first metatarsal angle ordinarily is zero. Any plantar deviation of the first metatarsal is indicative of a forefoot cavus deformity without varus and overactivity of the peroneus longus. A hindfoot cavus deformity, on the other hand, is characterized by excessive pitch of the calcaneal tuberosity greater than 20 to 30 degrees.
Cross-sectional imaging modalities have little role in the evaluation of CMT. While MRI will show fatty infiltration in the peroneus brevis and anterior tibialis, 9,29 the functional status of the muscle is better examined clinically.
CONSERVATIVE MANAGEMENT AND BRACING
There is no evidence that bracing of the foot in a patient with CMT can prevent progression of the foot deformities or maintain ambulatory capacity. Bracewear is best viewed as a tool for managing the current symptoms, usually dropfoot and ankle instability. Despite the absence of data, preventive measures can help avoid the fixed equinus deformity that may render the foot unbraceable. A program of gastrocsoleus stretching is appropriate.
Lateral ankle ligament laxity often is the presenting complaint in more active patients. A mild degree of dropfoot can be surprisingly well tolerated even in running athletes, who compensate simply by lifting their foot higher or circumducting the leg during the swing phase of gait. Inversion ankle sprains that occur without the dynamic protection of the peroneals are frequent and more difficult to prevent. A simple figure-of-eight Velcro strap ankle instability brace often is sufficient to assist these patients.
In those with more severe foot drop, a posterior spring-leaf ankle-foot orthosis (AFO) provides a dorsiflexion assist and has the advantages of being light-weight and easy to transfer between shoes. Patients who require more aggressive support of the ankle and hindfoot may benefit from a custom-molded leather boot brace or, for and obese patient, a conventional double-metal upright shoe-based AFO. The most effective brace for many patients is a custom-molded hinged AFO with dorsiflexion assistance. It is both light-weight and easily transferable from shoe to shoe. It directly corrects the dropfoot and lateral ankle instability while allowing some ankle motion for more efficient gait.
SURGICAL MANAGEMENT
Timing of Intervention
For moderately symptomatic patients with CMT, benefits to the patient must be weighed against the operative risks. In general, still-supple deformities are more easily corrected than later-stage rigid deformities. However, there presently are no data that directly address the timing of operative intervention. The decision to recommend surgery must be individualized for each patient. A summary of operative protocols for CMT-related foot deformities is shown in Table 4.
Soft-Tissue Corrections
A supple foot allows correction of the muscle imbalances directly. In addition to the commonly performed lengthening of the gastrocsoleus complex, a variety of other soft-tissue corrections can be done.
Complete release of the plantar fascia corrects the secondary contracture of the plantar fascia from a long-standing cavus deformity. Like many cavus foot procedures, it was first developed for patients with poliomyelitis by Arthur Steindler. 27 His operation, which involved completely removing the plantar fascia from its calcaneal origin, is still referred to as a “Steindler stripping.” Presently, the release is done roughly 1 cm distal to the origin of the plantar fascia. If marked adduction of the first ray also is present, the release can be extended to include the tight fascia of the abductor hallucis.
Transfer of the peroneus longus tendon to the peroneus brevis tendon can be done on the lateral border of the foot. The still-functional peroneus longus is detached just as it enters the cuboid groove. It is then woven in a Pulvertaft weave into the adjacent peroneus brevis just proximal to insertion. This serves two functions: it augments the weakened peroneus brevis in its eversion function while weakening the plantarflexion of the first ray that must be overcome by the weakened anterior tibial muscle.
Correction of a clawed hallux with a Jones transfer is another procedure from the era of polio surgery that is still useful. 8 In patients with sparing of the function of the EHL, it can be detached from the hallux and directly transferred into the first metatarsal neck. To avoid a floppy interphalangeal joint of the hallux, this joint usually is fused. This allows the EHL to directly dorsiflex the foot without causing a clawtoe deformity of the hallux. This deformity is particularly important to correct, because the dorsiflexion of the MTP joint of the hallux also forces the first ray down through the windlass mechanism of the plantar fascia, exacerbating the cavus of the forefoot.
The outcomes of soft-tissue surgery alone for CMT are surprisingly poorly documented. Most series of cases involve such a diverse group of patients, procedures, and outcomes that they are best viewed as expert opinion only (Level V evidence). 1,12,16 A single study by Roper and Tibrewal 22 demonstrated no progression to triple arthrodesis in 10 patients treated with soft-tissue procedures only at an average 14-year followup (Level IV evidence). This currently constitutes the only data to suggest that early operative intervention can prevent late fixed deformity.
The Jones transfer in patients with cavus foot deformities was retrospectively reviewed by Tynan et al. 30 (Level IV evidence). They indicated that the procedure adequately relieved symptoms due to the clawing of the hallux; however, it left residual symptoms from overload of the first ray in almost 50% of patients. Therefore, they recommended it as an adjunctive procedure only rather than as an isolated procedure.
Osteotomies as Adjunctive Procedures
Many feet affected by CMT fall into a middle ground: they have some supple features but have one or two rigid features that also require correction. In these patients, specific osteotomies can be used to avoid fusion. The osteotomies described are done in addition to and not as a replacement for the mandatory soft-tissue balancing.
Deformity, Motor Imbalance, and Surgical Options in CMT
A dorsiflexion osteotomy of the first ray is used when a fixed plantarflexion deformity of the first ray has developed. The osteotomy usually is made 1.5 cm distal to the MTC joint. It effectively elevates the first metatarsal head and directly affects the forefoot cavus deformity.
The Dwyer calcaneal osteotomy is a laterally-based closing wedge osteotomy of the calcaneus that swings the calcaneal tuberosity into valgus. 14 It is used when some motion remains in the subtalar joint but the calcaneus fails to correct out of varus.
The Samilson osteotomy was originally described for polio patients with a high calcaneal pitch angle. 24 It uses a crescentic osteotomy through the tuberosity of the calcaneus through which the tuberosity segment is rotated superiorly. In practice, a flat cut with rigid internal fixation can be used for CMT patients with a high-pitch angle; the tuberosity fragment is allowed to slide dorsally. It has the additional advantage that a lateral wedge also can be taken to combine the Dwyer and Samilson osteotomies into one biplanar cut.
Although frequently used, the long-term outcomes of adjunctive osteotomies in patients with CMT remain essentially unreported. Paulos et al. 20 reported 85% acceptable short-term results in a pediatric population that had combination of soft-tissue releases, tendon transfers, and forefoot ostetotomies (Level IV evidence). Followup, however, was limited to 2 years.
Fusions
Triple arthrodesis remains a mainstay of treatment for a severely affected rigid cavovarus foot. For the most severe deformities, a step-cut method of triple arthrodesis was described by Siffert 26 to more dramatically reduce the height of the arch, but this rarely is required. More limited fusions of the hindfoot usually are not applicable in patients with CMT because of the progressive nature of the deformity.
Ankle arthrodesis should be considered only rarely, because most patients with severe ankle arthrosis also have severe hindfoot deformity. Pantalar arthrodesis may be the only option. Total ankle replacement in patients with neurogenic cavus foot deformities has no documented success and should be avoided. Early failure of the prostheses is caused by the uneven wear on the medial side of the component and the extreme difficulty in achieving ligamentous balance around the ankle.
More literature is available documenting the results of triple arthrodesis in CMT than any other single treatment. All studies are case series (Level IV evidence). Wetmore and Drennan 31 reported a 21-year followup of triple arthrodesis in adolescents with CMT. Almost half of the feet had a poor ultimate result with recurrent deformity and bracewear; 20% eventually had pantalar arthrodesis. Mann and Hsu 15 reported a 25% incidence of recurrent deformity around the fusion and a 25% talonavicular nonunion rate. Other reports are more positive, including 88% good or excellent functional results 10 years postoperatively in a study by Wukich and Bowen. 32 Similar good results were reported by Santavirta et al. 25 at a 14-year followup. Notably, soft-tissue procedures were done as necessary in their study.
On balance, the literature indicates that triple arthrodesis in an adolescent with CMT should be viewed with some caution because of the prospect of recurrent deformity around the fusion. 15 When a fusion is necessary, strong consideration should be given to adding tendon balancing procedures, because this may reduce the possibility of recurrent deformity of the severity of recurrence.
SUMMARY
CMT is now recognized as a heterogeneous disease with multiple potential genetic alterations responsible for the condition. Genetic testing is available for the most common forms and can provide some information about prognosis.
Half of all cases of CMT represent new mutations, and the orthopaedic surgeon usually does not make the initial diagnosis.
CMT can be compatible with a remarkably high activity level and even athletic success early in life. Appropriate bracewear can be effective in maintaining patient function, but has not been shown to prevent progression of deformity.
All forms of CMT demonstrate electrical abnormalities in early childhood, are inexorably progressive, and eventually lead to the development of fixed contractures of the foot.
The classic CMT foot deformities result from characteristic muscle imbalances. These deformities include: clawtoes due to the long toe motors (extrinsics) over-powering the weak short toe motors (intrinsics); a forefoot cavus (plantarflexed first ray) secondary to a persistent peroneus longus muscle working against a weak anterior tibial muscle; hindfoot varus due to a retained posterior tibial muscle working against a weak peroneus brevis; and equinus contracture or dropfoot due to a functioning gastrocsoleus versus a weak anterior tibial muscle.
The ideal timing for operative intervention in CMT remains ill-defined. Earlier intervention allows still-supple deformities to be corrected with soft-tissue procedures and extraarticular osteotomies. The ultimate longevity of these procedures has not been established.
Operative management of CMT requires systematically identifying each major motor imbalance and contracture in the hindfoot, midfoot, and forefoot. Rigid deformities require either fusion or extraarticular osteotomies, more supple deformities usually can be corrected with soft-tissue surgery.