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Case Analysis : Case Analysis for Charcot-Marie-Tooth Disease

Case Analysis for Charcot-Marie-Tooth Disease(May 26th, 2015)

By Like Wu, Xiaojuan Wang, Sherry Xi, Bo Cheng, Susan Chu

Wu Medical Center

The patient is 34-year-old female. She was presented with involuntary movement of fingers and extremities prior weakness for the past 13 years without any apparent cause. The disease progressed gradually. She had nerve biopsy and gene analysis at a local hospital and was diagnosed with Charcot-Marie-Tooth disease (CMT). She took vitamins without any improvement. Her four limbs were weak. Her balance was bad. She always falls because of bad balance and lower limbs weakness. She had difficulty to hold objects. The distal ends of four limbs were depauperated, numbness and painful.

Physical examination:
The general examination was normal. Her speech and spirit was good. The cranial nerves was normal. The distal ends of four limbs were depauperated. The proximal end muscle power of both upper limbs was at level 4, the distal ends muscle power of both upper limbs was at level 3, and the muscle power of all fingers was at level 3-. The proximal end muscle power of both lower limbs was at level 4. The distal ends muscle power of both lower limbs was at level 3. The muscle tension of four limbs was normal. The tendon reflex of four limbs disappeared, the pathology sign was negative. The deep and shallow sensation of her four limbs distal ends were not good.

Diagnosis: Charcot-Marie-Tooth disease (CMT)

Treatment target: Replace the heredodegeneration nerve cells with normal stem cells to repair the nerves, improve the nerve function, and also to improve equilibrium function and motor function.

Treatment procedure and results:
We gave the patient 4 times neural stem cells (NSCs) and 4 times mesenchymal stem cells (MSCs) implantation treatment. The stem cells were activated in the patient’s body to repair the nerve damage. Together with nourishment of the neurons, improvement of circulation and regulating the immune, daily rehabilitation training was incorporated. During the treatment, the patient was happy, had a regular eating and sleeping pattern. With our doctor’s help, she was able to complete the treatment. After the treatment, the patient had significant improvement, her four limbs had less pain, numbness and weakness. Her exercise tolerance was better. The proximal end muscle power of both upper limbs was at level 5-. The distal ends muscle power of both upper limbs was at level 4, the muscle power of all fingers was at level 4-. The proximal end muscle power of both lower limbs was at level 5-. The distal ends muscle power of both lower limbs was at level 4-. Her balance and coordinate movement were better. Her life had been noticeably improved.

Charcot-Marie-Tooth disease (CMT) is also called Hereditary Motor and Sensory Neuropathy (HMSN), it has visible heredity. The main clinical characteristics: the distal ends of four limbs has progressive weakness, atrophia and sensory disturbance. CMT is one of the most common hereditary peripheral neuropathy (the incidence is around 1/2500). CMT is classified two types according to clinical and electrophysiological characteristics; CMT1 (demyelinating type) and CMT2 (axon type)

The patient had this disease when she was growing up, and the disease progressed slowly. She gradually had four limbs weakness, the distal ends of four limbs were depauperated, hypesthesia, tendon reflex of four limbs disappeared and balance disturbance. All the accessory examinations supported the diagnosis.

There is no useful treatment to this disease besides expectant treatment and supportive treatment. It couldn’t change the unusual nerve conduction or neural degeneration. Our center uses advanced NSCs transplantation technique to treats patients. The NSCs is used together with MSCs to make the imbedded NSCs increase the number of brain and spinal cord nerve cells, promotes nerve restoration and differentiation. At the same time, NSCs produces growth factors to protect damaged nerve cells. This technique was used in this patient and she recovered well, her life quality was improved. When the conventional therapy could not treat the disease, stem cell treatment is a new way to treat Charcot-Marie-Tooth disease and this brings hope to patients with this disease.

Hereditary Motor and Sensory Neuropathy (HMSN) :peripheral motor neuron and sensory nerve gene have pathological changes. The genetic material inside karyon changes, neurosome and cell membrane have transport dysfunctional. Cytoplasm and chondriosome’s function degenerated, the nerve cells die and drop out. The muscle and organs can’t control the nerves, they were palsied and depauperated. Because of nerve cells’ gene defect, the peripheral nerves cannot do self-repair. The number of nerve cells cannot be regenerated after it has decreased, there is no treatment methods in the world.

Our medical centre has new treatment plan and the plan can treat HMSN. Treatment idea: supplement nerve cells and replace abnormal cells with normal never cells. Formulate individualized plans for inpatients according to the patient’s incidence, time, clinical symptom’s relative, pathological condition and mode of inheritance to assort. We also give the patient rehabilitation evaluation according to our therapeutic data. It’s the new efficacious treatment method of the disease. This new method is a complex treatment and need the newest clinical technology to control.Include: 1.Improve the patient’s clinical symptom and the tissue’s pathological environment. This will contribute to the cells regeneration.2. NSCs located accurately, through diseased region signals induce gradient and get the lesion areas with neurotrophic factor concentration.3. The cells differentiate into targeting cells, so drugs we have can get the target.4. The expressive function of cells: even stem cell differentiates into that cell, it can’t express functionally in pathologic environment. We must use cell control technology to get a good result, get the right point of treatment and research only if we take subtle individual treatment plan. We have treated more than 20 patients and follow-up for 6 months. We found out that the disease was controlled and the motor function was better. That, for these reasons NSCs is a new way to treat the HMSN.

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Patient Stories:

Case Analysis : Stem Cell Therapy for Charcot-Marie-Tooth Disease

by Drs. Like Wu, Xiaojuan Wang and Bo Cheng

Charcot-Marie-Tooth disease is a group of hereditary disorders that damage the nerves in the arms and legs (peripheral nerves). Charcot-Marie-Tooth is also known as hereditary motor and sensory neuropathy.

The main signs and symptoms of Charcot-Marie-Tooth disease are muscle weakness and decreased muscle size. Patients may also notice a decreased sensation in those areas affected by the disease. Foot deformities such as hammertoes and high arches are common for patients suffering from Charcot-Marie-Tooth disease. Symptoms usually begin in the feet and legs, and they may eventually affect the hands and arms.

Muscle weakness and loss of balance can make walking difficult. Symptoms of Charcot-Marie-Tooth disease typically appear during adolescence or early adulthood, but this condition can develop during midlife as well.

Symptoms

Signs and symptoms of Charcot-Marie-Tooth disease may include:

Weakness in the legs, ankles and feet
Loss of muscle bulk in the legs and feet
High foot arches
Curled toes (hammertoes)
Decreased ability to run
Difficulty lifting the foot at the ankle (footdrop)
Awkward or higher than normal step (gait)
Frequent tripping or falling
Decreased sensation or a loss of feeling in the legs and feet

As Charcot-Marie-Tooth disease progresses, symptoms may not be limited to the feet and legs but may also involve the hands and arms. The severity of the symptoms can vary greatly from person to person. This is true even among family members.

Causes

Charcot-Marie-Tooth disease is a group of related conditions all caused by inherited mutations in genes involving the structure and function of the nerves that serve your feet, legs, hands and arms.

In some cases, these genetic mutations result in damage to the nerve itself. Other mutations damage the myelin sheath, the protective coating that surrounds the nerve. The end result, however, is the same — weaker messages traveling between your extremities and your brain.

That means some of the muscles in one’s feet may not receive the brain's signal to contract, so one is more likely to trip and fall. In addition, one’s brain may not receive pain messages from the feet, so if one has a blister on the toe, for example, it may get infected without one realizing it.

Pathologic Changes

Neurons, Schwann cells, and fibroblasts work together to create a working nerve. Schwann cells and neurons exchange molecular signals that regulate survival and differentiation. These signals are disrupted in CMT. Demyelinating Schwann cells cause abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction. The myelin sheath allows nerve cells to conduct signals faster. When the myelin sheath is damaged, nerve signals are slower, which can be measured by a common neurological test called electromyography. When the axon is damaged, on the other hand, this results in a reduced compound muscle action potential (CMAP).

Treatment progress

There currently is no effective drug to treat this disease. Moderate rehabilitation training can help maintain joint mobility. After more than 10 years of research, the Wu Stem Cell Medical Center (WSCMC) found that neural stem cells have good therapeutic effects on this disease. Neural stem cells can differentiate into functional neurons and myelin sheath, to repair a part of the damaged neural axon and myelin sheath, which improves the motor function of the patient. At the same time, these kinds of neural stem cells have the normal gene, so their genetic product can make up abnormal products of gene mutation of some patients, which can slow or stop the progress of disease. However, simply implanting stem cells to treat the disease has had no positive effect. Stem cell treatment also needs complicated regulation in vivo, including the cellular localization, differentiation and cellular functional expression in the body.

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