Nerve and Muscle (Studies in Biology)
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If the damage is severe, it can lead to serious problems such as falls, changes in heart rate, changes in blood pressure, difficulty breathing, paralysis, and even organ failure.
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The overall incidence of 2. Rieger has determined that, in the presence of paclitaxel, a widely used chemotherapeutic agent, peripheral neuropathy is caused by the increased expression of MMP matrix-metalloproteinase The disruptions to the intricate interactions between the skin and nerves caused by the increase in MMP activity are thought to contribute to paclitaxel-induced nerve damage. Rieger is now collaborating with the Mayo Clinic in Rochester, Minn. The hope, however, is that these drugs can also be used to treat other neuropathies or that the zebrafish model can be used to identify novel candidates for the treatment of other neuropathies.
In addition to chemotherapy, neuropathies can be caused by diabetes, multiple sclerosis, obesity, chronic kidney disease, aging and many other conditions, creating a huge unmet need for effective treatment. While drugs are available that provide partial relief of the pain associated with peripheral neuropathy, none address the underlying causes. The global market for pain-relieving drugs provides an indication of the size of this market. Nerve infiltration. During the procedure, two injections are conducted.
Nerve and Muscle (ALS)
First, intraneural infiltration A reaches the intrafascicular epineurium 2 and next, the perineural infiltration B is performed around the nerve. Throughout this section, we will describe the procedures to perform US-guided infiltrations of PRP in some nerves susceptible to peripheral lesions, namely median nerve Figure 4 , ulnar nerve Figure 5 and common peroneal nerve Figure 6. The infiltrations of the nerves mentioned in this section share a large number of key points, which are described below.
The details of each nerve are shown in Table 1. Median nerve infiltration. The median nerve is located by means of US in the area of the wrist A. Under US control with the probe placed in long-axis, the nerve blue is observed above the epiphyses of the distal radius red and lunate bone white B. The needle green is inserted in distal-proximal direction, and PRP is injected in an intraneural yellow and perineural way asterisk C.
Ulnar nerve infiltration. The ulnar nerve is located by means of US in the area of the elbow A. Under US control with the probe placed in long-axis, the nerve blue is observed above the epicondyle white B. In this case, the injection could be conducted in proximal-distal direction if the access is difficult.
Common peroneal nerve infiltration. Two approaches are possible to infiltrate common peroneal nerve. In the first approach, the nerve blue is located by US above the popliteal fossa with the US transductor in the long axis A and B. In the second approach, the nerve is located in the lateral side of the knee D. With the probe placed in the short axis, the nerve blue is observed above the peroneal head white and close to tibialis anterior muscle red E. In both cases, the needle green is inserted in proximal-distal direction, injecting PRP in an intraneural yellow and perineural way asterisk C and F.
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Preparation of the sterile field is required to maintain aseptic conditions throughout the treatment. The skin covering the affected nerve and the transducer of the US machine must be prepared following standard asepsis protocols. Prior to the infiltrations, the nerve must be located by means of US in the pertinent areas.
During this step, the US probe can be used in a long- as well as short-axis in respect to the nerve so that its examination can be as accurate as possible. In the course of PRP injections, the needle is placed parallel to the US probe, and consequently its orientation in respect to the nerve has influence on the PRP diffusion. With the transductor in the long-axis in respect to the nerve, the needle is introduced almost parallel to it, spreading PRP along the nerve.
If the US probe is placed in the short-axis, the needle is inserted at right angles to the nerve increasing the risk of injury axon. The spread is less than in the previous case, especially when the diameter of the nerve is large. However, this approach allows better visualization of the tissue. Therefore, we recommend using the US transductor that achieves a balance between diffusion and nerve visualization. The proximal-distal direction is preferable so that PRP spreads through the nerve. In some cases as injections into ulnar nerve, the direction can also be from distal to proximal zone if the injured area is unapproachable.
Both intraneural and perineural injections are performed during the treatment.
Activated PRP is injected softly and without rough movements of the needle to prevent nerve damage. As the PRP volume required for both infiltrations can exceed the capacity of the syringe, changes of syringes for loading them with PRP can be done without removing the needle from the injection site, thus avoiding repeated punctures. Firstly, it is advisable to perform the intraneural infiltration with the needle reaching the intrafascicular epineurium of the nerve. Once intraneural injection is accomplished, the needle is gently retreated placing it just above the nerve to conduct the perineural injection around the nerve.
The adjacent tissue to the nerve is detached when perineural infiltration is performed, appearing as a hypoechoic signal. This infiltration entails a hydrodissection that reduces nerve entrapment through a mechanical effect [ 42 ]. The dosage of these treatments is determined by the nerve size to be infiltrated, which is detailed in each case Table 1. In all cases, it is recommended to carry out two treatments, with an interval of two between both visits. The follow-up is conducted 4 weeks after finishing the treatment. Clinical examination is required in order to observe improvement in clinical parameters such as pain and paresthesia.
If the patient shows a significant improvement, no intervention will be performed. Six weeks after clinical follow-up, an electromyography EMG will be conducted to evaluate the state of the nerve and assess possible actions.
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When the patient evolution has flat-lined or is not enough, neural infiltrations with PRP will be repeated again. In case the patient has not experienced any improvement, infiltrations of PRP will be discarded and other treatment alternatives will be considered. An EMG study should be performed in the third month. PRP infiltrations into this nerve are indicated for compressive neuropathies such as pyramidal syndrome or deep gluteal syndrome.
The patient is placed as in the case of the sciatic nerve approach, namely in prone decubitus on a flat surface. By means of US control, the nerve is located at the level popliteal fossa, and then the nerve path is followed until gluteal fold, where PRP injection in distal-proximal direction is conducted.
If the nerve can be located in a more proximal area, the infiltration can also be performed following the proximal-distal direction. Traumatic neuroma follows different forms of nerve injury often as a result of surgery. They occur at the end of injured nerve fibers as a form of ineffective, unregulated nerve regeneration. Due to the peculiarities of these neuropathies, the volume of the product, the type of syringes and needles to infiltrate the PRP will largely depend on the nerve where the neuroma is located, which was described above.
In addition, not only an intraneural and a perineural injection into neuroma are conducted but also in the proximal nerve close to the neuroma.
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In many cases, surgical interventions are required for the treatment of neuropathies. Among these, the neurolysis is a standard procedure to separate the nerve from the surrounding tissues and try to solve problems related to compression and entrapment. In these cases, the use of PRP as a therapeutic adjuvant during surgery can stimulate and accelerate nerve recovery.
Next, both endoscopic Figure 7 and open neurolysis Figure 8 of a median nerve are explained. Neurolysis in other nerves will be done in the same way but adapting to the particularities of each nerve. Endoscopic neurolysis of median nerve. Endoscopic camera and cannula are introduced into the wrist A. Carpal ligament asterisk is dissected and cut B. PRP is infiltrated into the nerve C and a fibrin clot is placed between the nerve and the ligament D. Open neurolysis of median nerve. Median nerve and the transverse carpal ligament are observed after incision A.
Once median nerve is released, PRP is injected B. Finally, fibrin membrane C is placed between the nerve and the ligament D. After performing a small incision at the level of wrist crease, a cannula is introduced in order to observe structures in the wrist as the transverse carpal ligament with an endoscopic camera. When the transverse carpal ligament is located and dissected, it is cut with endoscopic knife so that the median nerve is released. A fibrin clot is placed in the open carpal tunnel before suturing. An incision at the level of wrist crease is conducted. The incision must be large enough to observe and access to the median nerve and the transverse carpal ligament.
Next, the median nerve and the transverse carpal ligament are located and dissected. During the surgery, the median nerve is released by cutting the transverse carpal ligament and removing all the adhesions present along the nerve. Finally, intraneural and perineural injections of PRP are performed.
In addition, a fibrin membrane is placed between the nerve and the ligament, to later suture the incision. PRP products present a number of features that are quickening the application of this therapy in clinical practice, namely ease of use, reasonable biosafety and great versatility. Therefore, and although the PRP is still a recent technique, several clinical studies have emerging in the last decade Table 2.
As in other pathologies, pain is one of the main problems of patients who suffer from peripheral nerve injuries. PRP showed to be a promising therapeutic tool for the relief or reduction of pain associated with neuropathies. At 3 months of follow-up, the pain was significantly alleviated in 11 out of 14 patients according to VAS score.