Denervation

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This magnified image of type 2 muscle fibers shows denervation atrophy occurring at the white spaces at the top left and bottom center of the image. The white space represents a disruption of the nerve fibers, resulting in a loss of nerve supply to the muscle fibers. Denervation atrophy - intermed mag.jpg
This magnified image of type 2 muscle fibers shows denervation atrophy occurring at the white spaces at the top left and bottom center of the image. The white space represents a disruption of the nerve fibers, resulting in a loss of nerve supply to the muscle fibers.

Denervation is any loss of nerve supply regardless of the cause. If the nerves lost to denervation are part of the neuronal communication to a specific function in the body then altered or a loss of physiological functioning can occur. [1] Denervation can be caused by injury or be a symptom of a disorder like ALS, [2] post-polio syndrome, [3] or POTS. [4] [5] Additionally, it can be a useful surgical technique to alleviate major negative symptoms, such as in renal denervation. Denervation can have many harmful side effects such as increased risk of infection and tissue dysfunction. [6]

Contents

Causes

The loss of nerve supply can be caused by injury, disorders, or result from a surgical procedure.

Injuries

Denervation may be the result of nerve injury. The three main types of nerve injury are neurapraxia, axonotmesis and neurotmesis. These three types distinguish between the severity of the nerve damage and the potential for recovery after the damage. After an injury in which some nerves are damaged, the brain has shown capabilities in rewiring or rearranging neuronal circuitry. This plasticity allows for the brain to compensate for the loss in neuronal communication resulting from injury. [7]

Disorders

Denervation processes have a strong association with the symptoms seen in post-polio syndrome. Those with post polio syndrome are undergoing a constant process of denervation and reinnervation. This process occurs after acute poliomyelitis and leads to increased motor unit areas over time. The motor unit areas soon increase to a point where reinnervation is no longer possible causing an uncompensated denervation of motor units which leads to muscle atrophy and loss of muscular strength. Following an acute polio infection diagnosis symptoms such as fatiguability, general weakness and pain are believed to be correlated to muscle denervation. [8]

Much like post-polio syndrome, amyotrophic lateral sclerosis also has similar symptoms of motor neuron degeneration leading to general weakness and in some cases paralysis. The type of symptoms experienced can depend on which particular areas of the body experience the loss in nerve supply. This process of denervation is however different from post-polio syndrome in that it only involves upper and lower motor neuron degeneration and does not experience a process of constant reinnervation and denervation. [9]

Surgical procedures

In addition to peripheral nerve injury, denervation is used as a medical procedure for various benefits resulting from eliminating nerve supply to a specific area of the body. In renal denervation, the procedure involves using radio frequency or ultrasound to remove sympathetic nerve supply to the wall of the kidney with the intention of reducing blood pressure and treating chronic hypertension. [10] However, renal denervation is used less frequently in recent years due to new evidence suggesting that blood pressure is not significantly reduced after the procedure and there are even recommendations against using the procedure since there has been little proof to show that renal denervation leads to reduced blood pressure. [11]

Other prevalent surgical procedures involve intentionally reducing nerve supply to treat a variety of disorders. In a sympathectomy, a sympathetic ganglion is surgically removed to treat hyperhidrosis, or excessive sweating. [12] Surgical or radiologic denervation of the carotid sinus is used to treat Carotid Sinus Hypersensitivity. [13] In a vagotomy, the vagus nerve is surgically removed to treat peptic ulcer disease through reducing stomach acid. [14] In a rhizotomy, nerve fibers in the spinal cord are removed in the hopes of eliminating chronic muscle pain. [15]

Physiological differences

In regard to skeletal muscle denervation there are two distinct diagnoses: entrapment and compressive neuropathies or non-entrapment neuropathies. Entrapment and compressive neuropathy syndromes occur due to compression and/or constriction on a specific location for a segment of a single nerve or multiple nerve sites. This entrapment or compression can be diagnosed based on multiple factors including physical examination, electrodiagnostic test and clinical history. [16]

Following denervation, muscular atrophy and degeneration occurs within affected skeletal muscle tissue. Within the skeletal tissue is observable progressive loss of weight of denervated muscles as well as reduction in muscle fiber size and quantity. These muscles exhibit a slowing of contraction speed, a reduction of developed tension, and twitch force. [8]

Magnetic resonance imaging (MRI) and high-resolution ultrasonography (US) are two clinical imaging examinations performed to classify the different diagnoses. Ultrasonography is advantageous with the evaluation of peripheral nerve resolutions while Magnetic Resonance Imaging is more sensitive in regard to signal intensity changes of the muscle. [16]

Denervation affects the muscle activation process that is brought on by the development and propagation of an action potential and the ensuing release of calcium. It is found that there is an increase with calcium reuptake because of changes within sarcoplasmic reticulum morphology and structure. As a result, there is a decrease in amplitude and velocity of impulse conduction with an increase in muscle spike duration. [17]

In clinical and experimental studies there is an observed increase in muscle excitability in electrical currents involving chemical actions, while there is a decrease in excitability to current associated with electrical induction in denervated muscles. Changes in the resting membrane potential involving denervated muscles presents mild depolarization when a muscle contraction stimulus is present. While there is no immediate change involving resting and action potential, there is an increase with membrane resistance. After prolonged denervation, it is revealed that resting membrane potential over time is reduced while action potentials progressively decreased and become slower. Acetylcholine is a neurotransmitter that becomes supersensitive in the presence of denervated muscle. Upon injection of acetylcholine, a slower contractile response, which is drastically under action potential threshold, is elicited. [17]

Reinnervation possibilities

Denervated muscles have shown the ability to survive after periods of denervation or in the case of a damaged nerve. The size of the nerve and its ability to function can be maintained if it is electrically stimulated soon after denervation, in clinical experiments. home-based functional electrical stimulation has been shown to rescue muscles which have experienced severe atrophy as a result of denervation. [18] This process involves electrically stimulating the nerves innervating the affected part of the body, using electrodes placed on the skin.[ citation needed ]

For muscles that cannot be rescued via home-based functional electrical stimulation, an Italian study suggests that, at some point in the future, the following techniques may be applicable: they must first have induction and separation of autologous myogenic cells. This can be completed either by in vivo marcaine infiltration of muscle tissue that can then be grown in vitro, or have in vitro induction of autologous adipose tissue followed by selection of myogenic stem cells that can be recreated in vivo. The new autologous myogenic stem cells will be injected, proliferated and differentiated into new mature muscle fibers. Functional properties of these newly created muscle fibers will be induced via surface electrodes and an external neuromodulator. [18]

Related Research Articles

<span class="mw-page-title-main">Charcot–Marie–Tooth disease</span> Neuromuscular disease

Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).

<span class="mw-page-title-main">Carpal tunnel syndrome</span> Medical condition

Carpal tunnel syndrome (CTS) is a nerve compression syndrome associated with the collected signs and symptoms of compression of the median nerve at the carpal tunnel in the wrist. Carpal tunnel syndrome is an idiopathic syndrome but there are environmental, and medical risk factors associated with the condition. CTS can affect both wrists.

<span class="mw-page-title-main">Post-polio syndrome</span> Human disease

Post-polio syndrome is a group of latent symptoms of poliomyelitis (polio), occurring at about a 25–40% rate. They are caused by the damaging effects of the viral infection on the nervous system and typically occur 15 to 30 years after an initial acute paralytic attack. Symptoms include decreasing muscular function or acute weakness with pain and fatigue. The same may also occur years after a nonparalytic polio infection.

Pudendal nerve entrapment (PNE), also known as Alcock canal syndrome, is an uncommon source of chronic pain in which the pudendal nerve is entrapped or compressed in Alcock's canal. There are several different types of PNE based on the site of entrapment anatomically. Pain is positional and is worsened by sitting. Other symptoms include genital numbness, fecal incontinence and urinary incontinence.

Diabetic neuropathy includes various types of nerve damage associated with diabetes mellitus. The most common form, diabetic peripheral neuropathy, affects 30% of all diabetic patients. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves. Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.

<span class="mw-page-title-main">Peripheral neuropathy</span> Nervous system disease affecting nerves beyond the brain and spinal cord

Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropathies affecting motor, sensory, or autonomic nerve fibers result in different symptoms. More than one type of fiber may be affected simultaneously. Peripheral neuropathy may be acute or chronic, and may be reversible or permanent.

Axonotmesis is an injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory functions distal to the point of injury are completely lost over time leading to Wallerian degeneration due to ischemia, or loss of blood supply. Axonotmesis is usually the result of a more severe crush or contusion than neurapraxia.

Meralgia paresthetica or meralgia paraesthetica is pain or abnormal sensations in the outer thigh not caused by injury to the thigh, but by injury to a nerve which provides sensation to the lateral thigh.

<span class="mw-page-title-main">Nerve conduction velocity</span> Speed at which an electrochemical impulse propagates down a neural pathway

In neuroscience, nerve conduction velocity (CV) is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factors, which include age, sex, and various medical conditions. Studies allow for better diagnoses of various neuropathies, especially demyelinating diseases as these conditions result in reduced or non-existent conduction velocities. CV is an important aspect of nerve conduction studies.

<span class="mw-page-title-main">Chronaxie</span> Electrophysiology metric

Chronaxie is the minimum time required for an electric current double the strength of the rheobase to stimulate a muscle or a neuron. Rheobase is the lowest intensity with indefinite pulse duration which just stimulated muscles or nerves. Chronaxie is dependent on the density of voltage-gated sodium channels in the cell, which affect that cell's excitability. Chronaxie varies across different types of tissue: fast-twitch muscles have a lower chronaxie, slow-twitch muscles have a higher one. Chronaxie is the tissue-excitability parameter that permits choice of the optimum stimulus pulse duration for stimulation of any excitable tissue. Chronaxie (c) is the Lapicque descriptor of the stimulus pulse duration for a current of twice rheobasic (b) strength, which is the threshold current for an infinitely long-duration stimulus pulse. Lapicque showed that these two quantities (c,b) define the strength-duration curve for current: I = b(1+c/d), where d is the pulse duration. However, there are two other electrical parameters used to describe a stimulus: energy and charge. The minimum energy occurs with a pulse duration equal to chronaxie. Minimum charge (bc) occurs with an infinitely short-duration pulse. Choice of a pulse duration equal to 10c requires a current of only 10% above rheobase (b). Choice of a pulse duration of 0.1c requires a charge of 10% above the minimum charge (bc).

A neurectomy, or nerve resection is a neurosurgical procedure in which a peripheral nerve is cut or removed to alleviate neuropathic pain or permanently disable some function of a nerve. The nerve is not intended to grow back. For chronic pain it may be an alternative to a failed nerve decompression when the target nerve has no motor function and numbness is acceptable. Neurectomies have also been used to permanently block autonomic function, and special sensory function not related to pain.

Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain.

<span class="mw-page-title-main">Superior cluneal nerves</span>

The superior cluneal nerves are pure sensory nerves that innervate the skin of the upper part of the buttocks. They are the terminal ends of the L1-L3 spinal nerve dorsal rami lateral branches. They are one of three different types of cluneal nerves. They travel inferiorly through multiple layers of muscles, then traverse osteofibrous tunnels between the thoracolumbar fascia and iliac crest.

<span class="mw-page-title-main">Ulnar neuropathy at the elbow</span> Medical condition

Idiopathic ulnar neuropathy at the elbow is a condition where pressure on the ulnar nerve as it passes through the cubital tunnel causes ulnar neuropathy. The symptoms of neuropathy are paresthesia (tingling) and numbness primarily affecting the little finger and ring finger of the hand. Ulnar neuropathy can progress to weakness and atrophy of the muscles in the hand. Symptoms can be alleviated by the use of a splint to prevent the elbow from flexing while sleeping.

<span class="mw-page-title-main">Ulnar neuropathy</span> Medical condition

Ulnar neuropathy is a disorder involving the ulnar nerve. Ulnar neuropathy may be caused by entrapment of the ulnar nerve with resultant numbness and tingling. It may also cause weakness or paralysis of the muscles supplied by the nerve. Ulnar neuropathy may affect the elbow as cubital tunnel syndrome. At the wrist a similar neuropathy is ulnar tunnel syndrome.

<span class="mw-page-title-main">Pronator teres syndrome</span> Medical condition

Pronator teres syndrome is a compression neuropathy of the median nerve at the elbow. It is rare compared to compression at the wrist or isolated injury of the anterior interosseous branch of the median nerve.

<span class="mw-page-title-main">Nerve compression syndrome</span> Human medical condition

Nerve compression syndrome, or compression neuropathy, or nerve entrapment syndrome, is a medical condition caused by chronic, direct pressure on a peripheral nerve. It is known colloquially as a trapped nerve, though this may also refer to nerve root compression. Its symptoms include pain, tingling, numbness and muscle weakness. The symptoms affect just one particular part of the body, depending on which nerve is affected. The diagnosis is largely clinical and can be confirmed with diagnostic nerve blocks. Occasionally imaging and electrophysiology studies aid in the diagnosis. Timely diagnosis is important as untreated chronic nerve compression may cause permanent damage. A surgical nerve decompression can relieve pressure on the nerve but cannot always reverse the physiological changes that occurred before treatment. Nerve injury by a single episode of physical trauma is in one sense an acute compression neuropathy but is not usually included under this heading, as chronic compression takes a unique pathophysiological course.

<span class="mw-page-title-main">Median nerve palsy</span> Medical condition

Injuries to the arm, forearm or wrist area can lead to various nerve disorders. One such disorder is median nerve palsy. The median nerve controls the majority of the muscles in the forearm. It controls abduction of the thumb, flexion of hand at wrist, flexion of digital phalanx of the fingers, is the sensory nerve for the first three fingers, etc. Because of this major role of the median nerve, it is also called the eye of the hand. If the median nerve is damaged, the ability to abduct and oppose the thumb may be lost due to paralysis of the thenar muscles. Various other symptoms can occur which may be repaired through surgery and tendon transfers. Tendon transfers have been very successful in restoring motor function and improving functional outcomes in patients with median nerve palsy.

<span class="mw-page-title-main">Smile surgery</span> Surgical procedure to restore smile

Smile surgery or smile reconstruction is a surgical procedure that restores the smile for people with facial nerve paralysis. Facial nerve paralysis is a relatively common condition with a yearly incidence of 0.25% leading to function loss of the mimic muscles. The facial nerve gives off several branches in the face. If one or more facial nerve branches are paralysed, the corresponding mimetic muscles lose their ability to contract. This may lead to several symptoms such as incomplete eye closure with or without exposure keratitis, oral incompetence, poor articulation, dental caries, drooling, and a low self-esteem. This is because the different branches innervate the frontalis muscle, orbicularis oculi and oris muscles, lip elevators and depressors, and the platysma. The elevators of the upper lip and corner of the mouth are innervated by the zygomatic and buccal branches. When these branches are paralysed, there is an inability to create a symmetric smile.

<span class="mw-page-title-main">Pathophysiology of nerve entrapment</span>

Nerve entrapment involves a cascade of physiological changes caused by compression and tension. Some of these changes are irreversible. The magnitude and duration of the forces determines the extent of injury. In the acute form, mechanical injury and metabolic blocks impede nerve function. In the chronic form, there is a sequence of changes starting with a breakdown of the blood-nerve-barrier, followed by edema with connective tissue changes, followed by diffuse demyelination, and finally followed by axonmetesis. The injury will often be a mixed lesion where mild/moderate compression is a combination of a metabolic block and neuropraxia, while severe compression combines elements of neuropraxia and axonmetesis.

References

  1. ↑ Forster, H. V. (2003-02-01). "Invited Review: Plasticity in the control of breathing following sensory denervation". Journal of Applied Physiology. 94 (2): 784–794. doi:10.1152/japplphysiol.00602.2002. ISSN   8750-7587. PMID   12531915.
  2. ↑ Kwan, Thaddaeus; Kazamel, Mohamed; Thoenes, Kristina; Si, Ying; Jiang, Nan; King, Peter H. (2020-10-07). "Wnt antagonist FRZB is a muscle biomarker of denervation atrophy in amyotrophic lateral sclerosis". Scientific Reports. 10 (1): 16679. doi: 10.1038/s41598-020-73845-z . ISSN   2045-2322. PMC   7541525 . PMID   33028902. S2CID   222209385.
  3. ↑ Jubelt, B.; Cashman, N. R. (1987). "Neurological manifestations of the post-polio syndrome". Critical Reviews in Neurobiology. 3 (3): 199–220. ISSN   0892-0915. PMID   3315237.
  4. ↑ Lei, Lucy Y.; Chew, Derek S.; Sheldon, Robert S.; Raj, Satish R. (2019-05-01). "Evaluating and managing postural tachycardia syndrome". Cleveland Clinic Journal of Medicine. 86 (5): 333–344. doi: 10.3949/ccjm.86a.18002 . ISSN   0891-1150. PMID   31066664. S2CID   147705420.
  5. ↑ Haensch, Carl-Albrecht; Tosch, Marco; Katona, Istvan; Weis, Joachim; Isenmann, Stefan (December 2014). "Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome". Muscle & Nerve. 50 (6): 956–961. doi:10.1002/mus.24245. ISSN   1097-4598. PMID   24647968. S2CID   3301605.
  6. ↑ Quinn, M. J. (2011-11-01). "Origins of Western diseases". Journal of the Royal Society of Medicine. 104 (11): 449–456. doi:10.1258/jrsm.2011.110014. ISSN   0141-0768. PMC   3206721 . PMID   22048676.
  7. ↑ Cotman, Carl W.; Berchtold, Nicole C. (1998-01-01). "Plasticity and growth factors in injury response". Mental Retardation and Developmental Disabilities Research Reviews. 4 (3): 223–230. doi:10.1002/(sici)1098-2779(1998)4:3<223::aid-mrdd10>3.0.co;2-x. ISSN   1098-2779.
  8. 1 2 Gonzalez, Henrik; Olsson, Tomas; Borg, Kristian (June 2010). "Management of postpolio syndrome". The Lancet Neurology. 9 (6): 634–642. doi:10.1016/s1474-4422(10)70095-8. PMID   20494327. S2CID   44657605.
  9. ↑ "Millennium Web Catalog". 0-hmg.oxfordjournals.org.libus.csd.mu.edu. Retrieved 2016-04-01.[ dead link ]
  10. ↑ Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M (December 2010). "Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial". The Lancet. 376 (9756): 1903–1909. doi:10.1016/s0140-6736(10)62039-9. PMID   21093036. S2CID   22838976.
  11. ↑ Lobo, Melvin D.; Belder, Mark A. de; Cleveland, Trevor; Collier, David; Dasgupta, Indranil; Deanfield, John; Kapil, Vikas; Knight, Charles; Matson, Matthew (2015-01-01). "Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension". Heart. 101 (1): 10–16. doi:10.1136/heartjnl-2014-307029. ISSN   1468-201X. PMC   4283620 . PMID   25431461.
  12. ↑ Cai, Song-Wang; Shen, Ning; Li, Dong-Xia; Wei, Bo; An, Jun; Zhang, Jun-Hang; Cai, Song-Wang; Shen, Ning; Li, Dong-Xia (March 2015). "Compensatory sweating after restricting or lowering the level of sympathectomy: a systematic review and meta-analysis". Clinics. 70 (3): 214–219. doi:10.6061/clinics/2015(03)11. ISSN   1807-5932. PMC   4449481 . PMID   26017654.
  13. ↑ https://www.ncbi.nlm.nih.gov/books/NBK559059/ [ bare URL ]
  14. ↑ Lagoo, Janaka; Pappas, Theodore N.; Perez, Alexander (January 2014). "A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease". The American Journal of Surgery. 207 (1): 120–126. doi:10.1016/j.amjsurg.2013.02.012. PMID   24139666.
  15. ↑ Niemistö, Leena; Kalso, Eija; Malmivaara, Antti; Seitsalo, Seppo; Hurri, Heikki (2003). "Radiofrequency Denervation for Neck and Back Pain: A Systematic Review Within the Framework of the Cochrane Collaboration Back Review Group". Spine. 28 (16): 1877–1888. doi:10.1097/01.brs.0000084682.02898.72. PMID   12923479. S2CID   44963601.
  16. 1 2 Connor, S.E.J.; Chaudhary, N.; Fareedi, S.; Woo, E.K. (August 2006). "Imaging of muscular denervation secondary to motor cranial nerve dysfunction". Clinical Radiology. 61 (8): 659–669. doi:10.1016/j.crad.2006.04.003. PMID   16843749.
  17. 1 2 Midrio, Menotti (2006-08-03). "The denervated muscle: facts and hypotheses. A historical review". European Journal of Applied Physiology. 98 (1): 1–21. doi:10.1007/s00421-006-0256-z. ISSN   1439-6319. PMID   16896733. S2CID   1993670.
  18. 1 2 Carraro, Ugo; Boncompagni, Simona; Gobbo, Valerio; Rossini, Katia; Zampieri, Sandra; Mosole, Simone; Ravara, Barbara; Nori, Alessandra; Stramare, Roberto (11 March 2015). "Persistent muscle fiber regeneration in long term denervation. Past, present, future". European Journal of Translational Myology. 25 (2): 77–92. doi:10.4081/ejtm.2015.4832. ISSN   2037-7452. PMC   4749009 . PMID   26913148.
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