Charcot Marie Tooth disease (CMT) also known as Chacot-Marie-Tooth hereditary neuropathy, peroneal muscular atrophy, and hereditary motor and sensory neuropathy, is a group of disorders that affect the peripheral nerves — the nerves that carry messages between the brain and muscles throughout the body. It is named after the three doctors who described it in 1886: Jean Martin Charcot and Pierre Marie in Paris, and Howard Henry Tooth in Cambridge, England. Charcot-Marie-Tooth disease is also sometimes referred to as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy.
CMT is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. A typical feature includes weakness of the foot and lower leg muscles, which may result in foot drop and a high-stepped gait with frequent tripping or falls. Foot deformities, such as high arches and hammertoes (a condition in which the middle joint of a toe bends upwards), are also characteristic due to weakness of the small muscles in the feet. In addition, the lower legs may take on an “inverted champagne bottle” appearance due to the loss of muscle bulk. Later in the disease, weakness and muscle atrophy may occur in the hands, resulting in difficulty with fine motor skills. Some patients experience pain, which can range from mild to severe.
The periphery nerves – the ones affected – are located outside the main central nervous system. Periphery nerves control muscles, as well as relaying data from our arms and legs to our brain, which allow us to sense touch. The building block of the nervous system is the nerve cell, or neuron. Neurons from the brain or spinal cord send electrical impulses down nerve fibres from the spinal cord to the muscles. The nerve fibres, which are like fibres in an electrical cable, are called ‘axons’. Axons are protected by an insulating material called myelin. Each axon is covered in a sheath of myelin, which keeps the axon healthy and helps electrical impulses travel quickly down nerve fibres.
CMT either interferes with the production of proteins that make up the myelin sheath, or else affects the structure or function of the axon. Neuropathies that affect myelin are known as ‘demyelinating’ neuropathies. Those that affect primarily the nerve fibres are called ‘axonal’ neuropathies. The result of both is that affected nerves cannot work properly to control movement or sensation.
Causes
Nerve Damage – A nerve cell communicates information to distant targets by sending electrical signals down a long, thin part of the cell called the axon. In order to increase the speed at which these electrical signals travel, the axon is insulated by myelin, which is produced by another type of cell called the Schwann cell. Myelin twists around the axon like a jelly-roll cake and prevents the loss of electrical signals. Without an intact axon and myelin sheath, peripheral nerve cells are unable to activate target muscles or relay sensory information from the limbs back to the brain.
Genetic Factors – CMT is caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath. Although different proteins are abnormal in different forms of CMT disease, all of the mutations affect the normal function of the peripheral nerves. Consequently, these nerves slowly degenerate and lose the ability to communicate with their distant targets. The degeneration of motor nerves results in muscle weakness and atrophy in the extremities (arms, legs, hands, or feet), and in some cases the degeneration of sensory nerves results in a reduced ability to feel heat, cold, and pain.
The gene mutations in CMT disease are usually inherited. Each of us normally possesses two copies of every gene, one inherited from each parent. Some forms of CMT are inherited in an autosomal dominant fashion, which means that only one copy of the abnormal gene is needed to cause the disease. Other forms of CMT are inherited in an autosomal recessive fashion, which means that both copies of the abnormal gene must be present to cause the disease. Still other forms of CMT are inherited in an X-linked fashion, which means that the abnormal gene is located on the X chromosome. The X and Y chromosomes determine an individual’s sex. Individuals with two X chromosomes are female and individuals with one X and one Y chromosome are male.
Types of CMT
There are various types of CMT:
- CMT 1 – the genes involved in myelin sheath production are faulty. The myelin sheath gradually wastes away. Approximately one third of all CMT cases are of this type.
- CMT 2 – Approximately 17% of all CMT cases. The defect is in the axon itself.
- CMT 3 – Also known as Dejerine-Sottas disease. This is a rare type of CMT. The myelin sheath is affected. The patient experiences severe muscle weakness and his/sense of touch is also affected severely. Children with CMT 3 may have noticeable symptoms.
- CMT 4 – also affects the myelin sheath. CMT 4 is rare. Experts believe several different genetic processes are involved in the development of CMT 4, but they are not sure which genes. Symptoms generally appear during childhood. Wheelchairs are commonly required by patients with CMT 4.
- CMT X – this type of CMT is caused by an X-chromosome mutation. This type of CMT is more commonly diagnosed in male patients. If female patients have CMT X, symptoms will be very mild. Approximately one tenth of all CMT cases in the UK are of this type.
Symptoms
CMT is a highly variable condition, even between members of the same family so the symptoms described here may not apply to all people with CMT.
In the most common types of CMT, symptoms usually begin before the age of 20 years and the typical symptoms are –
- Weakness and wasting of muscle in the lower legs and feet
- High arches in the feet (known medically as pes cavus) and curled toes
- Foot drop (inability to hold foot horizontal)
- Numbness in the feet
- Difficulty with balance
- Hand weakness and numbness, often appearing as much as ten years after foot and leg problems
- Fatigue as a result of the extra effort required to perform daily activities.
Common Symptoms
- Foot deformity (very high arched foot/feet)
- Difficulty lifting foot at the ankle (foot drop)
- Curled toes (known as hammer toes)
- Loss of lower leg muscle, which leads to skinny calves
- Numbness or burning sensation in the feet or hands
- “Slapping” when walking (feet hit the floor hard when walking)
- Weakness of the hips, legs, or feet
- Leg and hand cramps
- Loss of balance, tripping, and falling
- Difficulty grasping and holding objects and opening jars and bottles
The muscles that support the foot while walking are among the first to be affected by CMT so the first noticeable signs are often difficulty in walking because of problems picking up the feet. The toes drop as the foot is lifted, causing a tendency to trip and an awkward walking style. Children with CMT may be described as clumsy or not good at sport before any other symptoms are noticed.
High arched feet can lead to instability of the foot and ankle, with twisting of the ankles becoming very common. Curled or hammer toes are a very common symptom and can result in pain from ill-fitting shoes.
Pain is often a feature of CMT, and is usually a result of poor walking putting additional stress on the knees, hips, back and even shoulders and neck. More rarely, the damaged nerves themselves cause pain, known as neuropathic pain. Some people with CMT experience tremor in both the arms and legs. Severe tremor and CMT is given the name ‘Roussy-Levy Syndrome’.
Symptoms can progress noticeably at the time of the growth spurt associated with puberty.
Some very rare symptoms of CMT include; curvature of the spine (scoliosis) and speech, swallowing and breathing difficulties, particularly when lying flat in bed at night.
Complications
- Breathing – if the nerves that control the diaphragm are affected the patient may feel out of breath.
- Depression – the mental stresses, anxieties and frustrations of living with a progressive disease, such as CMT, can eventually raise the risk of developing depression.
- CBT (cognitive behavioral therapy) – CBT has been shown to help patients with CMT cope better. CBT trains the patient to react differently to his/her condition.
Treatment
Although there is no cure for CMT, therapies can treat the symptoms. The development of a comprehensive treatment plan with a health care team can help people with CMT lead an active life. Treatment plans generally involve one or more of the following:
Physical and occupational therapy – Therapists work to improve muscle strength and stamina and to help people complete tasks of daily living.
Braces and other orthopedic devices – Custom shoes or shoe inserts (foot orthoses) help to improve walking ability – Leg braces prevent ankle sprains and improve walking ability.
Surgery – For some people, surgery can help prevent or reverse foot and joint deformities.
- Osteotomy – used to correct severe flat feet. The surgeon either repositions or removes bones in the foot. After the operation the foot will be in plaster for a number of weeks.
- Arthrodesis – used to correct flat feet, relieve joint pain, and correct heel deformities. The three main joints in the back of the feet are fused, resulting in a stronger foot, better shape, and often less pain. After surgery the foot will be placed in a cast for a number of weeks. It can take up to 10 months before the foot recovers completely.
- Planter fascia release – inflamed tendons can cause continuous heel pain. Part of the tendon is surgically removed, while the remaining tendon is repositioned. The patient’s foot will be in a cast for about 3 weeks.
Pain management – Pain-killing drugs may be prescribed for people who have severe pain. Joint and muscle pain – resulting from stresses that are placed on parts of the body because of CMT.
NSAIDs (non-steroidal anti-inflammatory drugs), such as ibuprofen, can help reduce joint and muscle pain –
- Neuropathic pain – caused by damaged nerves (less common).
- NSAIDs can sometimes help alleviate the symptoms of neuropathic pain.
- TCAs (tricyclic antidepressants) – if NSAIDs are not effective, the patient may be prescribed a TCA. TCAs, although originally designed to treat patients with depression, are also effective in alleviating neuropathic pain symptoms.
Alternative Treatment
Coenzyme Q10 has already been studied in other diseases which involve deterioration of nerve cells. Coenzyme Q10 supplementation is safe and beneficial in a relatively small group of patients with Charcot-Marie-Tooth disease.
Creatine is one of the main symptoms of Charcot-Marie-Tooth disease muscle weakness and the supplement Creatine can help to improve muscle performance and help to treat myopathies. Evidence suggests that Creatine can help to improve muscle strength and is very well tolerated.
Alpha Lipoic Acid has proven to help protect the nerves from the toxic chemicals throughout the body and can help to ease the burning and numbness sensations that often accompany Charcot-Marie-Tooth disease.
Vitamin C supplement can be very effective for helping to treat balance and physical performance issues in those who suffer from Charcot-Marie-Tooth disease. Studies also show that Vitamin C may help with prevention the disease progression and can help to promote normal myelination in the nerves.
Meditation – Techniques include specific postures, focused attention, or an open attitude toward distractions. People use meditation to increase calmness and relaxation, improve psychological balance, cope with illness, or enhance overall health and well-being.
Yoga – Various styles of yoga are used for healthy bone purposes. Yoga typically combines physical postures, breathing techniques, and meditation or relaxation. People use yoga as part of a general health regimen, and also for variety of health conditions.
Acupuncture – This is a family of procedures involving the stimulation of specific points on the body using a variety of techniques, such as penetrating the skin with needles that are then manipulated by hand or by electrical stimulation.
Cayenne is very healing, will equalize the blood pressure and increase stimulation. It also has calcium to help the body rebuild.
Curcumin – Abnormal activation of nuclear factor kappa B (NF-kappaB) probably plays an important role in the pathogenesis of CMT.
Reference –
http://www.aanem.org/Patients/Disorders/Charcot-Marie-Tooth-Disease
https://www.uihealthcare.org/charcot-marie-tooth-disease/
https://my.clevelandclinic.org/health/diseases_conditions/hic_Charcot-Marie-Tooth_Disorder
http://www.medicalnewstoday.com/articles/172056.php
http://www.mda.org.au/Disorders/Peripheral/CMT.asp
http://www.gpnotebook.co.uk/simplepage.cfm?ID=-1241120765
http://www.healthline.com/health/charcot-marie-tooth-disease
http://patient.info/doctor/charcot-marie-tooth-disease
http://www.webmd.com/brain/charcot-marie-tooth-disease