How Do These Symptoms Affect Quality of Life?
One of the most common complaints in people with CMT is weakness in the extremities, most commonly demonstrated in the distal legs and leading to foot drop and a steppage gait, ultimately causing difficulty walking.6 These issues are a cause of concern for fall risks as the patient ages and the disease progresses.
In addition to lower extremity weakness, many people with CMT experience upper extremity weakness. Common upper extremity complaints include hand weakness, tremor, weakened grip strength, and impaired manual dexterity.5 These difficulties cause limitations in daily activities such as handwriting, buttoning clothing, opening bottles, and using eating utensils.3
While the physical disabilities of CMT are commonly addressed, the emotional and social impairments of the disease are often neglected. Anecdotal reports note patient dissatisfaction regarding the loss of independence in performing daily activities, as well as with overall health. This can negatively affect social interactions and precipitate depression. Feelings of anger, guilt, fear, and negative self-esteem can also be observed. Though the physical symptoms of CMT are apparent, mental health and psychosocial impairments are often overlooked.7 This provides a pivotal opportunity for providers to be especially vigilant when screening and treating CMT.
CMT Patient Workup
When a patient complains of sensory loss and muscle weakness, it is important to consider the most common causes of neuropathy.
Initially, primary care providers should order laboratory testing including complete blood count, vitamin B12, folate, and fasting plasma glucose to rule out common causes of peripheral neuropathy such as vitamin B12 deficiency, folate deficiency, and diabetes. The next step involves magnetic resonance imaging (MRI) of the neck and/or lumbar area to rule out spinal cord compression causing sensory loss and weakness.8 When appropriate, primary care providers may refer to neurology for further studies.
A nerve conduction study (NCS) would be ordered by a neurologist to assess the pattern of slowing or decreased conduction in the extremities, providing indirect evidence of myelin dysfunction.9 The classification of CMT is primarily based on the results of an NCS. To identify CMT type, upper motor nerve conduction velocity (NCV) is measured. Normal NCV values vary widely, ranging from 45 to 65 m/s. In CMT1, the demyelination that occurs causes slowed conduction speeds to less than 38 m/s in upper limb motor nerves. In CMT2, NCVs are greater than 38 m/s, indicating little to no signs of demyelination.9
Severity of axonal damage and muscle fiber loss is demonstrated with decreases in compound muscle action potential amplitude (CMAP) for motor nerves, and with decreases in sensory nerve action potential (SNAP) for sensory nerves. Both CMT1 and CMT2 express reductions in CMAP and SNAP amplitudes along with axonal loss as the disease progresses.9
Other studies that could be ordered include electromyography (EMG),9 genetic testing, or a nerve biopsy.10 EMG will display signs of chronic denervation with muscle unit potentials of increased amplitude and duration.9 Nerve biopsies, although rarely used, can identify genetic mutations in sporadic forms of CMT. The characteristic findings on nerve biopsy in CMT1 patients with a PMP22 gene duplication — the most common genetic mutation in CMT — are known as “onion bulbs.”10 Genetic testing can help determine the specific gene mutation causing the disease to be expressed.
Assessing CMAP and SNAP amplitudes is a more effective way to monitor disease progression than assessing NCV. Furthermore, it has been found that motor and sensory NCV actually increase with patient age.11 This increase in NCV is believed to be caused by myelin thickness remodeling that occurs throughout adult life with CMT.
However, CMAP amplitudes decrease with disease progression and correlate more closely with CMT Examination Score (CMTES), a tool used to assess clinical disability in CMT.11 Healthcare providers should closely evaluate the amplitudes of CMAP and SNAP when assessing disease progression specifically, as opposed to nerve conduction velocities.
How to Manage CMT
Unfortunately, there is no cure for CMT. Treatment options are primarily supportive therapies that focus on treating the symptoms and improving quality of life.12
There are 2 approaches to treatment: conservative treatment and surgical treatment. Conservative treatment is employed in younger patients who retain adequate flexibility and muscle strength and show slower disease progression.13 Much of the current research on treatment options is geared toward treating lower extremity weakness rather than upper extremity weakness, due to foot and leg imbalance being the focal point of the disease.
One study of 9 patients with a clinical, genetic CMT diagnosis identified a potential rehabilitation protocol that includes muscle recruitment, stretching, and proprioceptive exercises to improve dexterity in upper limbs and overall quality of life.14 The study results showed an improvement in thumb opposition, tripod pinch, and handgrip, especially in the dominant hand.14 While the study demonstrated a significant positive correlation between rehabilitation and upper limb weakness, more studies exploring conservative management of the upper extremity must be conducted for more accurate results.
Conservative treatment options for the lower extremities consist of the use of insoles, orthotics, and physical therapy to maintain foot flexibility by stretching retracted structures in the foot. It is believed that conservative management can slow the progression of the foot deformity and possibly reverse it completely in milder cases.
It is recommended that people with CMT be fitted for ankle-foot orthoses, which can benefit pes cavus and improve foot drop symptoms. These orthoses have been shown to reduce the walking energy cost per unit of distance; that is, the orthoses resulted in a lower level of metabolic effort and improved mechanical efficiency, believed to be due to a reduction in steppage gait in these patients.15
A study comparing types of orthoses demonstrated increased gait velocity with polypropylene orthoses compared with silicone orthoses. However, silicone orthoses met goals more consistently and scored better in terms of comfort.16 These results are helpful when considering conservative treatment with the use of ankle-foot orthoses.
Because the deformities resulting from CMT often worsen, many believe surgical correction could be more beneficial in the early stages while the patient still has flexibility.10 With surgical treatment, the goal is to obtain a stable, plantigrade foot that provides the patient with flexibility and muscle strength. Surgical options for CMT depend on many factors, including quality of life, flexibility of the deformity, and absence of degenerative arthritis.
Soft tissue procedures, including medial plantar fasciotomy with or without tendon transfer of peroneus longus to brevis and the Jones procedure, are common.13 Tendon transfers are indicated with muscle imbalance and to prevent relapse. Osteotomies are recommended in patients with osteoarticular deformities of the feet that retain flexibility.
In more severe cases in patients with stiff, severely deformed feet, patients will undergo triple arthrodesis.13 All of these surgical options have specific indications and are chosen on an individualized basis. In other words, there is not 1 gold standard surgery used for all cases, but a wide variety of surgical options for each patient’s case. There is minimal to nonexistent evidence-based research on surgical options for treating upper extremity weakness.
While both ankle-foot orthotics and surgical procedures have shown positive results of improving quality of life, treatment should be employed on an individualized basis. The current practice is to start with more conservative treatments, and — if the patient is refractory to those — then to consider surgical options.