A Clinical comment on the effects of ReNerv in functional peripheral nerve recovery. Markham, Rod; Markham Ryan. for peripheral neuropathic sufferers to (No peer review conducted, three cases support the continued use of this therapy as only) an effective adjunct treatment to physiotherapeutic rehabilitation. A Clinical comment on the effects of ReNerv in Aim The aim of this study was to determine functional peripheral nerve whether any functional peripheral nerve recovery. recovery could be obtained by using a topically applied biochemical restorative lotion called ReNerv for the treatment of Abstract peripheral neuropathy. A recent study to derive a clinical comment found that ReNerv is particularly beneficial for motorbike peripheral nerve injured sufferers two Method Only two male former motorbike rider subjects of similar age were chosen for mechanically injured peripheral neuropathy and a diabetic neuropathic sufferer. Two and one elderly subject (70+) with diabetic subjects (Ss) with mechanically-cause neuropathy as there were no other suitable peripheral nerve injury were assigned to volunteers with medically documented receive ReNerv treatment by applying 2 mL evidence. A non-blind study was conducted of the lotion per day on either the foot or where ReNerv was given to them marked. hand. The subjects applied the lotion in the The smell was distinctive but the actual respective locations of numbness and within ingredients were unknown to them. The a 3-week period the symptoms of peripheral liquid base is a plant wax derived from neuropathy in both Ss diminished Simmondsia Chinensis. significantly. Physical and psychological measures were completed before and after Clinical definition and Background on intervention, and again at a one-month peripheral neuropathy: follow up. The results showed that the subjects improved physically, as assessed Clinical definition of peripheral neuropathy by reports of presence of a sense of touch, (PN): PN is a condition caused by damage pain, and feeling heat, and cold on the sole to the nerves in the peripheral nervous of the foot or back of the hand. The subjects’ system. The peripheral nervous system belief that their new sense of touch and includes nerves that run from the brain and temperature perception was controlled by spinal cord to the rest of the body. Many of chance happenings decreased significantly, these nerves are involved with sensation signifying not just improvement in their and feeling things such as pain, temperature conditions but also in their belief to be able and touch. Peripheral neuropathy is usually to manage their symptoms. However the felt at first as tingling and numbness in the data gave support to the notion that ReNerv hands and feet. Symptoms can be treated subjects showed significantly greater described as burning, shooting pain, improvement in physical perception via the throbbing, aching, and "feels like frostbite" skin and in one S in joint movement. And at or "walking on a bed of coals." 1 the follow-up measurement, the subjects maintained the improvement in the physical Therefore, a nerve injury can result in a state. The report concluded that although problem with a muscle or in a loss of the mechanically injured subjects sensation. In some people, it also causes experienced significant benefit they also pain. To understand nerve injury and reported some neuropathic pain having recovery, it is important to understand the decreased. The researchers stated that different types of nerve injury. The type of there is evidence of the benefits of ReNerv Page 1 of 5 By Markham, R., Markham R. A Clinical comment on the effects of ReNerv in functional peripheral nerve recovery. nerve injury will determine the type of treatment that will be generally needed. Nerve Recovery and Regeneration After nerve injury, the nerve will try to repair Nerve Anatomy itself by sprouting regenerating nerve units. As mentioned before, nerves connect the These regenerating units will then try to brain and spinal cord to the muscles and grow down the nerve to reinnervate (restore skin, giving one movement and feeling. If a nervous function to) muscle or skin. If they nerve injury occurs, there is an interruption make a correct connection – motor nerve to in the information being conveyed to the muscle or sensory nerve to skin – then skin or muscles to and from the brain. The recovery of muscle function and skin larger nerves in the arms and legs, which sensation will occur. However, if the are about the size of a pencil, are made up regenerating nerve fibres do not make a of tens of thousands of nerve fibers – similar correct connection, then no recovery will to the makeup of a telephone cable. The occur. nerve fibres are grouped together in bundles called fascicles. Some nerves – such as the Nerves regenerate at the rate of 1.1 median and ulnar nerves in the arm – have millimeter per day. Although sensation can motor and sensory fascicles, giving one both be regained even after long periods of movement and feeling in the hand. denervation (loss of nerve supply), muscle reinnervation will not occur after long Nerve Injury Classification System periods of time without nerve innervation Two nerve injury classification systems are (nerve supply). Therefore, it is necessary to outlined below. get nerve to muscle as quickly as possible if recovery will not occur on its own. * A first-degree injury, or neurapraxia, will Electromyography (EMG) tests will show recover within days after the injury, or it may muscle recovery before the muscles can be take up to three months. The recovery will seen contracting. If there is no evidence of be complete with no lasting muscle or recovery by three to six months after nerve sensory problems. injury, surgery usually is recommended. 2 * A second-degree injury, or axonotmesis, also will recover completely; however, the recovery will be much slower than with a Figure 1. shows the subdivisions of Sensory first-degree injury. Neurons (3), * A third-degree injury also will recover slowly; in addition, only partial recovery will Fibre Size Modality Myelination Type occur. The amount of recovery will depend on a number of factors; for example, the A- 13-20 Limb alpha Yes more scarring in the nerve, the more likely (I) micrometers proprioception the recovery won’t be as strong, and with Limb A-beta 6-12 the potential mismatching of sensory and (II) micrometers proprioception, Yes vibration, pressure motor fibers, the less likely it is that the A- nerve will fully recover. delta 1-5 Mechanical sharp Yes micrometers * A fourth-degree injury occurs when (III) there is dense scar tissue within the nerve, Thermal pain, 0.2-1.5 completely blocking any recovery. C (IV) mechanical No micrometers burning pain * A fifth-degree injury involves complete separation of a nerve, such as a cut nerve. (Both fourth- and fifth-degree injuries require Figure 1 surgery for recovery.) * A sixth-degree injury is a combination of The simplest definition of what constitutes other types of nerve injury. Recovery and diabetic peripheral neuropathy for day-to- treatment will vary depending on which day clinical practice was agreed on at an types of nerve injury are present. International Consensus Meeting for the Outpatient Management of Neuropathy and Page 2 of 5 By Markham, R., Markham R. A Clinical comment on the effects of ReNerv in functional peripheral nerve recovery. was described as "the presence of Nerve graft surgery offers a treatment option symptoms and/or signs of peripheral nerve for peripheral neuropathy. However for most dysfunction in people with diabetes after patients, this option is generally costly and exclusion of other causes." can cause loss of perception in the area where the nerve graft was taken. Long-term Diabetic neuropathy is classified into several outcomes presently rely on an integration of syndromes, each with a distinct pattern of exercise, lifestyle adjustment, physiotherapy involvement of the peripheral nerves; a and diet (with diabetic neuropathic suffers). patient often has multiple or overlapping Neurological care has been therefore central syndromes. to the treatment of these patient groups. Historically, neuropathy was accepted as a There are some drugs that can cause consequence rather than a cause of peripheral neuropathy. The risk of getting diabetes only after Marchal de Calvi's 1864 peripheral neuropathy can sometimes observations. increase when the drugs listed here are taken together. The drugs didanosine (ddI , Peripheral neuropathies have been Videx), zalcitabine (ddC, Hivid), and described in patients with primary (types 1 stavudine (d4T, Zerit) are causes of drug- and 2) and secondary diabetes of diverse related neuropathy. Other potential causes causes, suggesting a common etiologic are isoniazid (INH), ethambutol (Myambutol), mechanism based on chronic vincristine, metrodinazole (Flagyl), dapsone. hyperglycaemia. The undoubted contribution Drinking alcohol increases the risk of of hyperglycaemia has received strong neuropathy. Taking too much vitamin B6 support from the Diabetes Control and can also cause neuropathy. There have also Complications Trial (DCCT). been reports of neuropathy associated with the protease inhibitor indinavir (Crixivan). Neuropathies are characterized by a progressive loss of nerve fibres that can be There may be dangers of toxicity from local assessed noninvasively by several tests of anaesthetics as well. “The overwhelming nerve function, including electrophysiology, clinical experience is that correctly quantitative sensory testing, and autonomic administered local anaesthetics do not carry function tests. a risk of nerve injury. However, all local anaesthetics are potentially neurotoxic, and Pathologically, numerous changes have this may become apparent when the local been demonstrated in both myelinated and aesthetic is applied in unduly high unmyelinated fibres, although Schwann cell concentrations or at higher than normal time. changes may be the primary pathologic The potential for neurotoxicity with local change. 4 aesthetic is a function of its potency, concentration, and the length of exposure of A relatively higher frequency of the neuronal tissue to the agent. Exposure mechanically-caused peripheral nerve of the endoneurium to a very high injuries to the limbs among motorbike riders concentration of local anaesthetic may is expected due to the high level of the contribute to neurologic deficit. Under body’s exposure to the road environment, normal conditions, an injected bolus of local speed, and other factors. Motorbike anaesthetics expands until it reaches accidents tend to be more prevalent among pressure equilibrium and the surrounding males. People with such disabilities with tissues. While diffusing to the tissues, the sensory peripheral neuropathy also suffer interstitial fluid rapidly dilutes a local from social isolation and subsequent anaesthetic, and systemic absorption symptoms of depression contributing to assists in decreasing its concentration. reduce quality of life. The burden of However, this may not be the case during peripheral neuropathic rehabilitation falls intrafascicular injection with its concomitant largely within primary care services. trauma, neural ischemia, and possible Page 3 of 5 By Markham, R., Markham R. A Clinical comment on the effects of ReNerv in functional peripheral nerve recovery. vasoconstriction. Indeed, in several models continues to monitor her diet and takes of nerve injury and using a number of insulin injections. injectable agents, only intrafascicular injections resulted in a neurologic injury that Implementation can be documented as early as 30 minutes Dose: Only 2-3 mLs of ReNerv lotion was following intraneural injection. applied lightly on the affected area once a Intrafascicularly injected local-anaesthetic day where numbness was identified on Ss solutions lead to changes in the permeability body and allowed to be absorbed for a 45- of the blood-nerve barrier, associated minute period. oedema, increased endoneurial fluid pressure, and consequent nerve-fibre injury. Frequency: ReNerv was applied by pouring In contrast, extra-fascicular injection about 2 mLs out of a 50 mLs bottle once a produces little or no evidence of nerve day and every day for one to 28 days. injury.” 5 Timing: Usually it was applied about an hour Treatment plan before retiring to bed to sleep at night . Ss comprehension/active participation: We Compliance: Compliance was reported and had the required Ss comprehension/active accepted by the researcher. participation. Ss characteristics: Two Mechanically- Clinical signs: Within 15 minutes there was caused injuries (one being in the foot and a reported tingling feeling in the foot of an the other in the back of the hand) Ss (MCI) MCI. The other two Ss did not report this Age: late forties years; The MCI – foot has sensation. After a four week period, had sensory neuropathy for 16 months. The numbness in the extremities had MCI – hand had sensory neuropathy within “diminished significantly”. The sense of light four weeks. One female with Diabetic touch, heavy touch, temperature (hot and Peripheral Neuropathy in a foot Ss (DPN) cold) and pain sensation returned. MTAS Age: 70+ has had this condition for decades. was 10 for the MCI S in his hand; at least 7 MCIs had no feeling in the extremity of the for the MCI S for his foot, which started limb (foot or hand) the Markham Tactile gaining sensation on the third day of Scale Assessment (MTSA) of 1 for being the treatment; and at least 7 for DPN, which lowest level of perception to light and heavy was on the second day of treatment. touch. DPN had 5 out of 10 in MTSA. Laboratory markers Indication (the need for each drug) drug history: MCI Ss were initially on painkillers and discontinued after a number of weeks after the accident. DPN has been and still continues to have insulin injections. M suitable. onitoring the Ss for continuing suitability of drug/dose regimen: The current dose regimen appears Contraindication/interaction: There are no Signs/symptoms of effectiveness and contraindications or interactions with other toxicity: There did not appear to be any medications other than ReNerv helps also to signs/symptoms of toxicity as ReNerv is: promote more movement as reported by the topically applied on the skin; only a small MCI S with greater angle of foot movement. amount is used; it has active DPN has had no immunohistochemical-related constituents contraindications/interactions with ReNerv that can be safely taken even orally, and though she only needed it to be applied usually are metabolised by the liver and once only. kidney within a short period of time once they enter the blood stream. Continuity of care: The MCI Ss had rehabilitation after the accident for a number Ss compliance: Ss were compliant for the of weeks but this has discontinued. DPN experiment’s requirements. Page 4 of 5 By Markham, R., Markham R. A Clinical comment on the effects of ReNerv in functional peripheral nerve recovery. growth cones, nerve fibres and myelin Adjust choice of topical application dose: the sheath formation. There is an international Ss can do any adjusting of the topical dose patent pending on the formulation, the if Ss wish. No change of dosage was made. manufacturing process and delivery system. Advice/discouragement about over- Unwanted symptoms: There were no consumption of ReNerv: Due to the specific unwanted symptoms reported and none biochemical constituents, and the significant were expected. effects resulting from its use it appears safe enough and probably necessary to only use Recorded adverse reaction: There are no ReNerv for a short period of time. recorded adverse reactions to ReNerv by the Ss. Clinical outcome Therapeutic benefit: ReNerv appears to be a Conclusion suitable adjunct treatment for restoring ReNerv appears to be particularly beneficial relatively quickly peripheral nerve for sufferers of peripheral neuropathy of the functionality from a state of numbness extremities of the limbs in terms of associated with both diabetic peripheral restoration of peripheral nerve functionality. neuropathy and mechanically-caused It is not unexpected that this finding may peripheral neuropathy. The Ss applied have a direct impact on the number of nerve ReNerv in the respective locations of grafts performed, improved quality of life numbness and within a four-week period and cost savings in terms of medical found the symptoms of numbness in the treatment and the number and lengths of extremities of the limbs diminished hospital visits. significantly. Physical and psychological measures were completed before and after intervention, and again at a four-week follow-up. However the data revealed that Reference: the ReNerv treated MCI S-foot showed greater improvement in joint mobility of the 1. Peripheral Neuropathy - a Simple Fact Sheet from ankle, in the range of movement than before. the AIDS Treatment Data Network, And at the follow-up four week later, the Ss http://www.aegis.com/factshts/network/simple/neurop maintained the improvement in emotional .html, 10th April 2006 and psychological state. There was no 2. Nerve Injury and Recovery, Washington University subsequent medical treatment. Physicians Division of Plastic and Reconstructive Surgery There is evidence of the benefits of ReNerv Faculty for peripheral neuropathic sufferers to http://www.plasticsurgery.wustl.edu/PatientCare/Nerv support the continued use of this therapy as eInjury.asp, 10th April 2006 an effective adjunct treatment. The possible 3. Excerpt from Diabetic Neuropathy, WebMD, future clinical studies with diabetic www.wbmd.com, Omaha, Nebraska peripheral neuropathy and mechanically- http://www.emedicine.com/pmr/topic40.htm, 10th caused peripheral neuropathy may appear April 2006 to be worthwhile. 4. Excerpt from Diabetic Neuropathy, WebMD, www.wbmd.com, Omaha, Nebraska Safety: ReNerv lotion is safe to use topically http://www.emedicine.com/neuro/byname/diabetic- on the skin as the carrier oil of natural liquid neuropathy.htm, 10th April 2006 wax represents approximately 95% concentration of the ReNerv product, 5% 5. New York School of Regional Anesthesia, Manhattan, NY USA, Admir Hadzic concentration of Regenerin. Regenerin is a http://www.nysora.com/publications/complications/#to combination of active immunohistochemical- th xicity, 10 April 2006 related substances found to have particular roles in the functioning of schwann cells, Page 5 of 5 By Markham, R., Markham R.