Charcot Marie Tooth Disease
Charcot Marie Tooth disease (CMT) is a diverse group of hereditary neuropathies, initially included as the hereditary sensory and motor neuropathies. The disease has several subtypes with different modes of transmission, recessive or dominant, with different penetrance. CMT is characterized by inherited neuropathies without known metabolic derangements. Is divided in four types, Charcoth Marie Tooth type 1 (CMT 1) and Charcoth Marie Tooth type 2 (CMT 2) belong to the group of neurological impairment with neuronal demyelination. Charcot Marie Tooth type 3 (CMT 3) or Dejerine-Sottas disease and Charcot Marie Tooth type 4 (CMT 4) are included in the group of recessive hereditary neuropathies, which are sever demyelinating neuropathy, with onset in childhood.
Charcot Marie Tooth Disease Symptoms
Charcot Marie Tooth type 1 (CMT 1)
It is the most common form of disease, affecting 1 in 2,500 individuals, with an autosomal dominant transmission. The main signs of the disease are the distal paralysis of the legs which are visible from the first decade of life. Paralysis begins distal to the foot, then progressing to the lower third of the thigh, resulting in the characteristic stork leg or inverted champagne bottle appearance of the leg. Pes cavus (high-arch foot) could be the first sign of the disease. Paresis may also occur in the upper limb, with onset in small muscles of the hand, and later in the evolution of the disease, paralysis may spreads to the lower third of the forearm.
Sensory disorders are present and are characterized by polyneuritc symptoms without paraesthesia. Reflexes become diminished, and Achilles reflexe abolition occurs early in the evolution of the disease. In 30% of patients with CMT1 nerves are hypertrophic. Electrophysiological characteristic appearance of disease is a marked decrease of nerve conduction velocity at a speed of 30-40 m / sec in the upper limbs and at a speed of 10-20 m / sec in the lower limbs. Sural nerve biopsy is showing onion bulb formation hypertrophy and a density reduction of myelin fibers.
Charcot Marie Tooth type 2 (CMT2)
CMT 2 is less common than CMT 1 and the onset of the disease occurs in the second or third decade of life, and in rare cases CMT 2 may debut at old age. Paralysis are the first manifestations of the disease, being bilateral and symmetrical. Sensory disorders are present and are characterized by polyneuritic symptoms, being symmetrical, bilateral and with a distal onset. Achilles reflex is abolished. The disease has a slow, long evolution and nerve conduction velocity is normal. Cerebrospinal fluid has a normal quantity of protein. Sural nerve biopsy shows axonal loss, demyelination and onion bulb formation hypertrophy is less frequent.
Charcot Marie Tooth type 3 (CMT 3) or Dejerine-Sottas disease
CMT 3 has a recessive autosomal transmission. Peripheral neuropathy presents aspects similar to those of CMT 1, symptoms to which is added ataxia. Nerve conduction velocity is lower than in CMT 1, less than 12 m / sec, and the amount of protein in cerebrospinal fluid is increased. Nerve biopsy reveals marked onion bulb formation hypertrophy and hypomyelination of nerve fibers.
Charcot Marie Tooth type 4 (CMT 4)
CMT 4 is an autosomal recessive sensorymotor neuropathy, with a familial character.
Charcot Marie Tooth Disease Diagnosis
Imaging studies, like ultrasonography and MRI are useful in the diagnosis of CMT 1, but should be corroborated with elctromyography and nerve conduction study. MRI of the lower limb is useful in the assessment of patients with Chracot Marie Tooth neuropathies.
Electromyography and nerve conduction study are useful in diagnosis of demyelinating types of Charcot Marie Tooth disease such as CMT 1, showing a diffuse and uniform slowing of nerve conduction. Characteristic for CMT 1 is a marked decrease of nerve conduction velocity at a speed of 30-40 m / sec in the upper limbs and at a speed of 10-20 m / sec in the lower limbs, associated with compound motor action potential and amplitude of at least 0.5 millivolts. In Dejerine-Sottas disease (CMT 3) nerve conduction velocity is less than 10 m / sec, associated with congenital hypomyelination.
Genetic tests are available for some types of Charcot Marie Tooth disease. Approximately 70-80% of CMT 1 is caused by alteration of the PMP-22 gene, located on chromosome 17. Genetic alteration can be identified by pulsed field gel electrophoresis and fluorescent in situ hybridization (FISH).
Nerve biopsy is indicated only in cases of diagnosis dilemma. In CMT 1, are observed few myelinated fibers, and intramuscular nerves are surrounded by a rich connective tissue. Myelin is atrophic along the fibers and lamellar sheaths present concentric hypertrophy. Formation of the typical onion bulb is noted. In CMT 2, axonal degeneration is present. In Dejerine-Sottas disease, demyelination with thinning of the myelin sheath is a characteristic of the disease.
Charcot Marie Tooth Disease Treatment
Charcot Marie Tooth dose not dispose of a treatment which can reverse or slow the natural disease process, because non of the current drugs can correct myelin abnormalities, prevent its degeneration, or prevent axonal degeneration.
Patients must be evaluated and treated symptomatically by a team that includes a neurologist, physiatrist, orthopedic surgeon, physical therapist and a occupational therapist.
Pain is one of the most sever symptom of the disease and therefore should be combated. Musculoskeletal pain may be treated with nonsteroidal anti-inflammatory drugs and neuropathic pain may be treated with to tricyclic antidepressants or antiepileptic drugs, such as carbamazepine or gabapentin.
Orthopedic surgical interventions are required in order to correct pes cavus , scoliosis and other joint deformities. Orthopedic surgical procedures are represented by:
Interventions on soft tissue (plantar fascia release, tendon release or transfer);
Osteotomy (metatarsal, midfoot, calcaneal);
Joint stabilizing (triple arthrodesis).