Charcot-Marie-Tooth Disease (CMT)

• Charcot Marie Tooth (CMT) is a neurological and inherited condition.
• CMT is also known as hereditary motor and sensory neuropathy, manifesting as peripheral neuropathy.
• CMT is also called "Peroneal Muscular Atrophy"
• In CMT, the brevis muscle is most commonly affected, while the longus muscle is often spared.
• CMT is a hereditary and progressive condition characterized by neuropathy and muscle wasting.
• CMT affects either the axon (Type 2) or myelin sheath (Type 1) of nerves.
• CMT is the most common cause of cavovarus feet, affecting 1 in 2500 people.
• It was described in 1886 by Jean-Martin Charcot and Howard Henry Tooth.
• This discovery showed the link between the condition to an abnormal peripheral nervous system.
• CMT is caused by a gene defect on chromosome 17 or chromosome 1.
• Most commonly, it involves chromosome 17, specifically the PMP22 gene, influencing mitochondrial protein coding for neuronal proteins.
• The most common inheritance pattern is autosomal dominant (Type 1).
• 70-80% of patients have CMT 1, caused by an alteration in the PMP-22 gene on chromosome 17.
• Less common and more severe X-linked inheritance of type 1 CMT is often seen at an earlier age.
• Genetic inheritance features different CMT types, resulting in variable phenotypes and clinical severity.

Type 1 CMT

• Type 1 CMT is the more common type; 80% of patients have it.
• It follows an autosomal dominant transmission pattern
• With Type 1 CMT myelin surrounding the nerve is abnormal.
• Hypertrophic demyelinating neuropathy occurs, reducing nerve conduction due to myelin deficiency.
• Nerve conduction velocity is slowed (less than 38 m/s).
• Peak onset is in the 1st to 2nd decade of life or early childhood.
• Motor and sensory deficits are more severe in type 1.

Type 2 CMT

• Type 2 CMT involves axonal neuropathy with normal or near-normal nerve conduction velocity.
• The axonal amplitude or magnitude of the impulse is decreased.
• Less disabling with less sensory loss than type 1 and presents later in life.
• Type 2 CMT manifests through a loss of sensory and motor nerve response amplitudes.
• The rate impulse is normal, while the amplitude impulse is abnormal.

Type 3 CMT: Dejerine-Sottas Disease

• Type 3 CMT is a more severe form than CMT 1, with infantile onset.
• Severe demyelination with delayed motor skills is a characteristic of CMT3
• Often occurs without a family history.
• CMT 3 involves slow development of motor skills, loss of walking ability as an adult, hearing loss, and severe sensory problems.

CMT Pathology

• Loss of myelin and axons seen distally in the lower extremity.
• Intrinsic foot muscles, farthest down, are lost first, leading to hammer toes as longest nerves are affected first.
• Degenerative changes in spinal roots, anterior horn cells, and posterior column occur secondarily.
• Leg muscle degenerative changes from damage to motor fibers and anterior horn cells result in fatty infiltration or pseudohypertrophy.
• Hypertrophic nerves with onion-bulb formation are seen in dominantly inherited form (Type 1) of the disease.
• Nerve biopsy reveals concentric circles around nerves with demyelination followed by re-myelination for Type 1 СМТ.

Pathophysiology (Nerve Biopsy)

• Onset is marked by a decreased number of myelinated fibers in the peripheral nerves, enlarged endoneurium, and some posterior column degeneration.
• Demyelination (type 1) is marked by Schwann cells proliferating and forming concentric arrays of re-myelination.
• A thick layer of abnormal myelin around the peripheral axon is referred to as onion bulb appearance.
• CMT 1 has onion bulb formation while CMT 2 shows axonal loss with Wallerian degeneration, or breakdown of the nerve distal to the area where there is axonal loss.

Order of Muscle Degeneration

• The order features muscles supplied by long axons of the sciatic nerve being affected first.
• The first muscles affected are the intrinsic muscles of the foot, causing clawing of the toes due to the loss of stability at the metatarsophalangeal joints (MPJ).
• Hammertoe deformities can develop, with neurologic causes primarily associated with extensor substitution.
• The next group of muscles affected includes the extensor hallucis longus (EHL), extensor digitorum longus (EDL), and tibialis anterior.
• Tibialis anterior is impacted first, allowing the posterior muscles, particularly the Achilles tendon, to overpower it, leading to early equinus.
• Since tibialis anterior normally acts as an antagonist to peroneus longus, its weakness allows peroneus longus to remain active for a longer period. This results in excessive plantarflexion of the first ray, causing retrograde supination and further increasing cavus deformity.
• The peroneus brevis muscle is affected next, becoming overpowered by the intact posterior tibial tendon, which serves as its antagonist. Since the posterior tibial tendon is the main inverter of the foot, its unopposed function results in severe varus deformity.
• Without the opposition of tibialis anterior, peroneus longus becomes uninhibited and causes a severely plantarflexed first ray, leading to forefoot valgus. In response, rearfoot varus worsens as the body compensates for the forefoot valgus through midtarsal joint and subtalar joint supination.
• The triceps surae, consisting of the gastrocnemius and soleus muscles, is the last muscle group to be affected.

Muscle Imbalance:

• Weak anterior tibial muscle: Equinus
• Weak peroneus brevis muscle: Varus/Inversion
• P. L. and T.A. tendon forces the forefoot into increased pronation, and plantarflexed is increased
• P. B. and T.P. tendon create TP exaggerates RF varus, which means a medial shift of TN and CC joints and locks the MTJ in Supination
• Intrinsic muscle loss means a loss of activity of short foot muscles which leads to claw toes and extensor substitution of hammer toe.

Clinical Examination of CMT Patient

• Adolescent patients may exhibit pain-free symptoms but still have complaints about foot shape, increasing clumsiness and ankle sprains, and inability to participate in sports.
• In CMT, it is important to determine the underlying cause of cavovarus foot structure.
• Classic clinical findings include distal/bilateral muscular atrophy or an inverted champagne bottle.
• Pes Cavus Foot Structure (Equinovarus Foot structure) can be due to/indicated by peroneus brevis weakness
• Drop foot (Weak Tibialis Anterior Muscle) impacts gait leading to a steppage gait.
• Other clinical findings include weakness of foot/hand intrinsic muscles, peroneal muscle atrophy (PL relatively spared)
• Document muscle strength of all muscle groups in lower leg and appreciate the individuality of patients with CMT.
• Document whether there is Sensory Deformity/ Component to CMT and sensory findings.

Ankle Range of Motion (ROM)

• Ligamentous instability is a common finding and should be assessed during the exam.

Appearance of the Foot

• Clawing of the toes may be present, often associated with extensor substitution.
• Hindfoot varus can be identified by the medial concavity of the Achilles tendon
• The "Peek-A-Boo" heel sign may also be present when looking at the patient from the front, indicating a varus position of the subtalar joint.

Digital Deformity Pathogenesis

• Paralysis of the intrinsic muscles leads to the development of claw toes.
• Weakness of the anterior tibial muscle results in the need for extensor substitution, where the long extensors compensate to achieve adequate dorsiflexion during the swing phase of gait.
• Other types of hammertoe deformities include flexor substitution and flexor stabilization.

Coleman Block Test

• The Coleman Block Test is used to determine the degree of flexibility of the hindfoot in patients with cavus foot and helps guide treatment decisions.
• If the heel varus corrects to neutral or valgus, this indicates a flexible rearfoot compensating for a forefoot deformity and can be managed with orthotics
• If the heel maintains its varus position, this suggests a rigid structural rearfoot varus, which typically requires surgical correction of the rearfoot.

Anatomy of a Cavovarus Foot

• Hindfoot varus develops due to the overactivity of the posterior tibial tendon (PTT) as a result of a weak peroneus brevis (PB).
• Forefoot equinus is caused by the pull of the Achilles tendon due to weakness of the tibialis anterior (TA) and extensor digitorum longus (EDL).
• The first metatarsal becomes plantarflexed due to the action of the peroneus longus (PL), which remains uninhibited due to weak tibialis anterior, contributing to forefoot valgus.
• Pseudoequinus develops due to weak dorsiflexors with an intact Achilles tendon.

Potential Lab Studies

• Genetic testing may be useful in identifying some forms of disease.
• Electromyography (EMG) and nerve conduction velocity (NCV) studies can reveal decreased velocity and amplitude.
• Nerve biopsy, particularly of the sural nerve, is considered the best diagnostic test, as it commonly reveals an "onion bulb” appearance

Cavus Foot on Radiograph

• Radiographic findings associated with cavus foot deformity include a bullet hole sinus tarsi, a posteriorly displaced cyma line, and a plantarflexed first ray, leading to an increased Meary's angle.
• The fibula appears posterior to the tibia due to external rotation.
• Additional findings include decreased talar declination and increased calcaneal inclination.

Non-Surgical Treatments

• Flexible deformities are assessed using the Coleman block test and are initially managed with foot orthoses.
• These orthoses aim to elevate the lateral column and forefoot while allowing the first ray to bear weight on the ground, helping to maintain the subtalar joint in a neutral position.

Treatment Overview Surgical

Considerations:

• Motor Status of the Foot and Ankle: Determine which muscles are still viable and functioning.
• Flexibility of the Deformity: Flexible deformity: Treated with tendon transfers and osteotomies OR Rigid deformity: Requires arthrodesis (joint fusion).
• Degree of Sensory Impairment: Around 75% of patients have some sensory impairment, which can affect surgical decisions. Principles of Surgical Correction:
• The goal is to create a stable, pain-free, and functional limb.

Soft Tissue Surgery

Tendon Rebalancing

• The primary goal of tendon rebalancing is to address the deforming forces that affect the foot.
• These are often Peroneus Longus, Deep Posterior Muscle Group (specifically Posterior Tibial Tendon), AND/OR Achilles Tendon
• The goal of surgery is to weaken the deforming forces and strengthen the antagonistic muscles.
• This may involve rerouting strong (intact) deforming tendons to improve function.

Tendon Transfers

• Best Results: Tendon transfers are most effective in patients over 10 years old.
• Objectives of Tendon Transfer Surgery include considering the deforming forces acting on the foot, improving pronation forces, and improving dorsiflexion

Osseous Surgery

• Osteotomies are typically performed in the Calcaneus, Midfoot, or 1st Metatarsal to correct deformities.

Rearfoot Procedures

• The goal is to pull the rearfoot (RF) into a more neutral or valgus position.
• Dwyer Osteotomy a lateral base wedge is removed from the calcaneus, closing the wedge reduces varus and "slides" the heel laterally, AND this lateral displacement also lateralizes the insertions of the Achilles tendon.

###Lateral Displacement Calcaneal Osteotomy

• This involves a through-and-through osteotomy of the calcaneus
• The posterior tubercle is slid laterally, producing calcaneal valgus.
• This procedure puts the rearfoot into valgus and moves the Achilles tendon from the medial to the lateral side, reducing its supinatory strength.