Treatment can involve observation, repair, tendon transfers or nerve grafting depending on the acuity, degree of injury, and mechanism of injury. The authors conclude that MR imaging provides a sensitive method of evaluating wallerian degeneration in the living human brain. In the setting of neuropraxia, this chart assumes that the conduction block is persisting across the lesion and EMG findings listed are distal to the lesion in the relevant nerve territory. [10] Degeneration follows with swelling of the axolemma, and eventually the formation of bead-like axonal spheroids. If gliosis and Wallerian degeneration are present . MAPK signaling has been shown to promote the loss of NMNAT2, thereby promoting SARM1 activation, although SARM1 activation also triggers the MAP kinase cascade, indicating some form of feedback loop exists. Wallerian degeneration (the clearing process of the distal stump), axonal regeneration, and end-organ reinnervation. We report a 54 year old male patient, referred to our hospital for sudden-onset left hemiparesis. About the Disease ; Getting a Diagnosis ; . [45] Activation of SARM1 is sufficient to collapse NAD+ levels and initiate the Wallerian degeneration pathway.[44]. Question: QUESTION 1 Carpal tunnel and tarsal tunnel syndrome cause nerve degeneration resulting in specific symptoms and changes in the nerves. Axonal degeneration is followed by degradation of the myelin sheath and infiltration by macrophages. 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury. The effect of cool external temperatures slowing Wallerian degeneration in vivo is well known (Gamble et al., 1957;Gamble and Jha, 1958; Usherwood et al., 1968; Wang, 1985; Sea et al., 1995).In rats, Sea and colleagues (1995) showed that the time course for myelinated axons to degenerate after axotomy was 3 d at 32C and 6 d at 23C. neuropraxia) recover in shorter amount of time and to a better degree. The Wlds mutation is an autosomal-dominant mutation occurring in the mouse chromosome 4. [50] Specific mutations in NMNAT2 have linked the Wallerian degeneration mechanism to two neurological diseases. When the regenerating axon reaches the end organ, the axon matures and becomes myelinated. Paralysis and sensory loss develop acutely, but nerve conduction of the distal segment only remains intact until the distal segment is consumed by Wallerian degeneration. Copyright 2020. The possible source of error that could result from this is possible mismatching of the target cells as discussed earlier. [46] This relationship is further supported by the fact that mice lacking NMNAT2, which are normally not viable, are completely rescued by SARM1 deletion, placing NMNAT2 activity upstream of SARM1. Neuroimage. It is usually classified into four stages: The distribution of Wallerian degeneration depends on the region of injury and how it relates to white matter tracts that originate there. AIDP is the most common form of Guillain-Barr syndrome (GBS) in . Observed time duration for 8@ .QqB[@Up20i_V, i" i. Acute crush nerve injuries and traction injuries can be detected. The only known effect is that the Wallerian degeneration is delayed by up to three weeks on average after injury of a nerve. Schwann cell activation should therefore be delayed, as they would not detect axonal degradation signals from ErbB2 receptors. What will the . If soma/ cell body is damaged, a neuron cannot regenerate. [24] Macrophages also stimulate Schwann cells and fibroblasts to produce NGF via macrophage-derived interleukin-1. (2010) Polish journal of radiology. Chong Tae Kim, MD, Jung Sun Yoo, MD. Inoue Y, Matsumura Y, Fukuda T et-al. Regeneration is rapid in PNS, allowing for rates of up to 1 millimeter a day of regrowth. PNS is much faster and efficient at clearing myelin debris in comparison to CNS, and Schwann cells are the primary cause of this difference. Wallerian degeneration in the corpus callosum. Griffin M, Malahias M, Hindocha S, Khan WS. MeSH information . 0
A chemically similar drug in this class produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose. The macrophages, accompanied by Schwann cells, serve to clear the debris from the degeneration.[5][6]. Another factor that affects degradation rate is the diameter of the axon: larger axons require a longer time for the cytoskeleton to degrade and thus take a longer time to degenerate. The prolonged presence of myelin debris in CNS could possibly hinder the regeneration. [6] The process by which the axonal protection is achieved is poorly understood. When painful symptoms develop, it is important to treat them early (i.e . Nerve Structure: https://commons.wikimedia.org/w/index.php?curid=1298429. Therefore, most peripheral nerve injuries are initially are managed conservatively, with nerve function evaluation at 3 weeks via nerve conduction study and electromyography (NCS/EMG). Symptoms: This section is currently in development. Additionally, high resolution MRI (1.5 and 3 Tesla) can further enhance injury detection. Corresponding stages have been described on MRI. As axon sprouting and regeneration progress, abnormal spontaneous potentials decrease and MUAPs may appear variable. While Schwann cells mediate the initial stage of myelin debris clean up, macrophages come in to finish the job. During injury, nerves become more hyperintense on T2 and, given the chronicity, muscle atrophy may be present and localized edema canbeseen. NCS can demonstrate the resolution of conduction block or remyelination. Axonotmesis presents as enlarged hyperintensity with loss of fascicular structure, edema, Neurotmesis terminal neuroma, muscle atrophy, fatty replacement. Studies indicate that regeneration may be impaired in WldS mice, but this is likely a result of the environment being unfavorable for regeneration due to the continued existence of the undegenerated distal fiber, whereas normally debris is cleared, making way for new growth. David Haustein, MD; Mariko Kubinec, MD; Douglas Stevens, MD; and Clinton Johnson, DO. Schwann cells respond to loss of axons by extrusion of their myelin sheaths, downregulation of myelin genes, dedifferentiation and proliferation. A related process of dying back or retrograde degeneration known as 'Wallerian-like degeneration' occurs in many neurodegenerative diseases, especially those where . 1989;172 (1): 179-82. Muscle and tendon transfers can lead to adhesive scarring in the antagonist muscle and prevent proper tendon function. The distal nerve, particularly . All agents have been tested only in cell-culture or animal models. However, the reinnervation is not necessarily perfect, as possible misleading occurs during reinnervation of the proximal axons to target cells. CNS regeneration is much slower, and is almost absent in most vertebrate species. Axonal degeneration may be necessary pathophysiological process for serum CK elevation given that not just AMAN patients but also AIDP patients . In cases of cerebral infarction, Wallerian degeneration appears in the chronic phase (>30 days). Bassilios HS, Bond G, Jing XL, Kostopoulos E, Wallace RD, Konofaos P. The Surgical Management of Nerve Gaps: Present and Future. Wallerian degeneration is the process of antegrade degeneration of the axons and their accompanying myelin sheaths following proximal axonal or neuronal cell body lesions. In addition, recovery of injury is highly dependent on the severity of injury. [22] An experiment conducted on newts, animals that have fast CNS axon regeneration capabilities, found that Wallerian degeneration of an optic nerve injury took up to 10 to 14 days on average, further suggesting that slow clearance inhibits regeneration.[23]. The seminal discovery of the slow Wallerian degeneration mice (Wld) in which transected axons do not degenerate but survive and . Symptoms include progressive weakness and muscle wasting of the legs and arms. Some of the agents include erythropoietin, tacrolimus, acetyl-L-carnitine, N-acetylcysteine, testosterone, chondroitinase ABC, dimethylsulfoxide, transthyretin (pre-albumin), ibuprofen, melatonin, and polyethylene glycol. [37] These authors demonstrated by both in vitro and in vivo methods that the protective effect of overexpression of NMNAT1 or the addition of NAD+ did not protect axons from degeneration. . 09/20/2013. Both axonotmesis and neurotmesis involve axonal degeneration but there are differences in the process and prognosis of axonal recovery. [1] A related process of dying back or retrograde degeneration known as 'Wallerian-like degeneration' occurs in many neurodegenerative diseases, especially those where axonal transport is impaired such as ALS and Alzheimer's disease. Because peripheral neuropathy most frequently results from a specific disease or damage of the nerve, or as a consequence of generalized systemic illness, the most fundamental treatment involves prevention and control of the primary disease. Open injuries with nerve in-continuity (epineurium intact), and all closed-injuries, initially are managed conservatively, with nerve function evaluation at 3 weeks via nerve conduction study and electromyography (NCS/EMG). 4. Coleman MP, Conforti L, Buckmaster EA, Tarlton A, Ewing RM, Brown MC, Lyon MF, Perry VH (August 1998). [7] Within 4 days of the injury, the distal end of the portion of the nerve fiber proximal to the lesion sends out sprouts towards those tubes and these sprouts are attracted by growth factors produced by Schwann cells in the tubes. [45] The SARM1 protein has four domains, a mitochondrial localization signal, an auto-inhibitory N-terminus region consisting of armadillo/HEAT motifs, two sterile alpha motifs responsible for multimerization, and a C-terminus Toll/Interleukin-1 receptor that possesses enzymatic activity. Wallerian degeneration is a process of antegrade neural disintegration that develops after injury to the proximal axon or cell body. Y]GnC.m{Zu[X'.a~>-. However, only complement has shown to help in myelin debris phagocytosis.[14]. A recent study pointed to inflammatory edema of nerve trunks causing ischemic conduction failure, which in the ensuing days can lead to Wallerian-like degeneration [19, 20]. The most commonly observed pattern is an injury to the precentral gyrus (such as may be seen in an MCA infarct) with resultant degeneration of the corticospinal tracts. Macrophage entry in general into CNS site of injury is very slow. After the 21st day, acute nerve degeneration will show on the electromyograph. US National Library of Medicine.National Institutes of Health.2015; 51(2): 268275. Get Top Tips Tuesday and The Latest Physiopedia updates, The content on or accessible through Physiopedia is for informational purposes only. Axonal degeneration occurs either as a primarily axonal process or as a bystander-type axonal degeneration, associated with . The activated macrophages clear myelin and axon debris efficiently, and produce factors that facilitate Schwann cell migration and axon . In experiments conducted on rats,[18] myelin sheaths were found for up to 22 months. Motor symptoms, which include any changes related to movement, are frequently present with mononeuropathies. 8-13 The cerebral peduncle is ideal for assessing postinfarction wallerian degeneration . Site: if the muscle is very deep or limited by body habitus,MRI could be a better option than EMG. Because the epineurium remains intact . David Haustein, MD, MBANothing to Disclose, C. Alex Carrasquer, MDNothing to Disclose, Stephanie M. Green, DONothing to Disclose, Michael J. Del Busto, MDNothing to Disclose, 9700 W. Bryn Mawr Ave. Ste 200 These. %%EOF
Incidence. Polyethylene glycol (PEG) has proven successful in animal models and was applied to human trials. Read more, Physiopedia 2023 | Physiopedia is a registered charity in the UK, no. This website uses cookies to improve your experience while you navigate through the website. Whereas conventional magnetic resonance imaging fails to detect signal intensity changes until four weeks after stroke, diffusion tensor imaging (DTI) reveals changes related to WD only after days. On the contrary, axonotmesis and neurotmesis take longer to recover and may not recover as well, or at all. These require further exploration and clinical trials: The current standards of care for peripheral nerve injury is based on serial examinations and/or electrodiagnostics. PEG helps fuse cells, develop desired cell lines, remove water at the injured lipid bilayer, and increase the fusion of axolemmal ends. However, if the injury is at the end of the axon, at a growth of 1mm per day, the distal segment undergoes granular disintegration over several days to weeks and cytoplasmic elements begin to accumulate.[3]. DWI:high signal on DWI and low signal on ADChave been demonstrated along the affected white matter tracts, from the first days after insult until 8 months after 7. The cleaning up of myelin debris is different for PNS and CNS. European Journal of Neuroscience, 2: 408-413. glial cell line-derived neurotrophic factor, nicotinamide mononucleotide adenylyltransferase 1, Connective tissue in the peripheral nervous system, "Wallerian degeneration, wld(s), and nmnat", "Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons", "NMNAT: It's an NAD + Synthase It's a Chaperone It's a Neuroprotector", Current Opinion in Genetics & Development, "Experiments on the Section of the Glossopharyngeal and Hypoglossal Nerves of the Frog, and Observations of the Alterations Produced Thereby in the Structure of Their Primitive Fibres", "An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse", "Nerve injury, axonal degeneration and neural regeneration: basic insights", "Endocytotic formation of vesicles and other membranous structures induced by Ca2+ and axolemmal injury", "Axon degeneration: molecular mechanisms of a self-destruction pathway", "Multiple forms of Ca-activated protease from rat brain and muscle", "Microanatomy of axon/glial signaling during Wallerian degeneration", "Complement depletion reduces macrophage infiltration and ctivation during Wallerian degeneration and axonal regeneration", "Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents", "Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central nervous system: the dorsal radiculotomy model", "Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection", "Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts", "Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth", https://doi.org/10.1111/j.1460-9568.1990.tb00433.x, "A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4", "Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses in vivo", "A local mechanism mediates NAD-dependent protection of axon degeneration", "NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration", "Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo", 10.1002/(SICI)1096-9861(19960729)371:3<469::AID-CNE9>3.0.CO;2-0, "dSarm/Sarm1 is required for activation of an injury-induced axon death pathway", "Sarm1-mediated axon degeneration requires both SAM and TIR interactions", "Resolving the topological enigma in Ca 2+ signaling by cyclic ADP-ribose and NAADP", "SARM1 activation triggers axon degeneration locally via NAD destruction", "+ Cleavage Activity that Promotes Pathological Axonal Degeneration", "S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy", "Pathological axonal death through a MAPK cascade that triggers a local energy deficit", "MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2", "Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1", https://en.wikipedia.org/w/index.php?title=Wallerian_degeneration&oldid=1136392406. This condition has two main causes: 1) degenerative diseases affecting nerve cells, such as Friedreich's disease, and 2) traumatic injury to the peripheral nerves. Charcot-Marie-Tooth disease (CMT) is the umbrella term for a range of inherited genetic conditions affecting the peripheral nervous system (the nerves stretching from the spinal cord to the muscles). The axon then undergoes a degeneration process that can be anterograde or orthograde (Wallerian) [1] or retrograde. Schwann cells and endoneural fibroblasts in PNS. But opting out of some of these cookies may have an effect on your browsing experience. Innovative treatment of peripheral nerve injuries: combined reconstructive concepts. axon enter cell cycle thus leading to proliferation. The peripheral nervous system includes all nerves and ganglia located outside of the brain and spinal cord and is comprised of both the somatic and autonomic nervous systems. If a sprout reaches the tube, it grows into it and advances about 1mm per day, eventually reaching and reinnervating the target tissue. If you believe that this Physiopedia article is the primary source for the information you are refering to, you can use the button below to access a related citation statement. Validation of Temporal Development of Tactile Allodynia It occurs between 7 to 21 days after the lesion occurs. 6. In contrast to PNS, Microglia play a vital role in CNS wallerian degeneration. Injury and electrodiagnostic findings are time dependent and therefore, it is suggested to delay these studies for several weeks to better witness specific findings and delineate injury severity. [34][35], The mutation causes no harm to the mouse. Entry was based on first occurrence of an isolated neurologic syndrome . 2004;46 (3): 183-8. Sullivan R, Dailey T, Duncan K, Abel N, Borlongan CV. Sunderland grades 1-3 are treated with conservative measures while grades 4-5 usually require surgical repair. Injuries to the myelin are usually the least severe, while injuries to the axons and supporting structures are more severe (Fig 2). The fact that the enhanced survival of WldS axons is due to the slower turnover of WldS compared to NMNAT2 also helps explain why SARM1 knockout confers longer protection, as SARM1 will be completely inactive regardless of inhibitor activity whereas WldS will eventually be degraded. If the sprouts cannot reach the tube, for instance because the gap is too wide or scar tissue has formed, surgery can help to guide the sprouts into the tubes. [26] Schwann cells upregulate the production of cell surface adhesion molecule ninjurin further promoting growth. Symptoms Involvement of face, mouth, trunk, upper limbs, or muscle Disease associations IgM antibodies vs TS-HDS; Patients treated with vincristine predictably develop neuropathic symptoms and signs, the most prominent of which are distal-extremity paresthesias, sensory loss, . MR-pathologic comparisons of wallerian degeneration in spinal cord injury. Wallerian degeneration in response to axonal interruption 4. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. [27] These lines of cell guide the axon regeneration in proper direction. Pierpaoli C, Barnett A, Pajevic S et-al. After this, full passive and active range of motion may be introduced for rehabilitation. Visalli C, Cavallaro M, Concerto A et al. 5-7 In either case, the volume loss does not become visible until at least several months poststroke. However, research has shown that this AAD process is calciumindependent.[11]. For example, retrograde and anterograde degeneration [such as Wallerian degeneration (Pierpaoli et al. It is noteworthy that these TAD-like lesions do not come with classic Wallerian-type axonal degeneration and evolve through a dose limiting manner [12,13,14]. Mice belonging to the strain C57BL/Wlds have delayed Wallerian degeneration,[28] and, thus, allow for the study of the roles of various cell types and the underlying cellular and molecular processes. Forty-three patients with wallerian degeneration seen on MR images after cerebral infarction were studied. Nerve conduction studies (NCS): Delayed conduction (prolonged distal latency, conduction block, and/or slow conduction velocity) across the lesion but normal conduction distal to the lesion. Due to lack of such favorable promoting factors in CNS, regeneration is stunted in CNS. With cerebral softening, there are varied symptoms which range from mild to catastrophic. Calcium plays a role in the degeneration of the damaged axon during Wallerian degeneration, [29][30] The gene mutation is an 85-kb tandem triplication, occurring naturally. These include: Select ALL that apply. [11], These findings have suggested that the delay in Wallerian degeneration in CNS in comparison to PNS is caused not due to a delay in axonal degeneration, but rather is due to the difference in clearance rates of myelin in CNS and PNS. Early changes include accumulation of mitochondria in the paranodal regions at the site of injury. However, their recruitment is slower in comparison to macrophage recruitment in PNS by approximately 3 days. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JO, White LE. approximately one inch per month), but individual nerves may have different speeds (ulnar, 1.5 mm/day; median, 2-4.5 mm/day; and radial, 4-5 mm/day). In many . [39] However, once the axonal degradation has begun, degeneration takes its normal course, and, respective of the nervous system, degradation follows at the above-described rates. Similarly . Another key aspect is the change in permeability of the blood-tissue barrier in the two systems. Needle electromyography (EMG): normal spontaneous activity but may show decreased motor unit action potential (MUAP) recruitment due to conduction block. Ducic I, Fu R, Iorio ML. [31], Although the protein created localizes within the nucleus and is barely detectable in axons, studies suggest that its protective effect is due to its presence in axonal and terminal compartments. Purpose of review: Diffuse or traumatic axonal injury is one of the principal pathologies encountered in traumatic brain injury (TBI) and the resulting axonal loss, disconnection, and brain atrophy contribute significantly to clinical morbidity and disability. After the 21st day, acute nerve degeneration will show on the electromyograph. A novel therapy to promote axonal fusion in human digital nerves. 16 (1): 125-33. AJNR Am J Neuroradiol. support neurons by forming myelin that encases nerves. If any of your symptoms worsen or change after your physical exam, it is important to follow-up with your health care provider. Diffusionweighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) map in a patient with a large parietooccipital lobar intracerebral hemorrhage, showing reduced diffusion (bright on DWI and dark on ADC) in the splenium of the corpus callosum from Wallerian degeneration. The recruitment of macrophages helps improve the clearing rate of myelin debris. 75 (4): 38-43. Unable to process the form. They finally align in tubes (Bngner bands) and express surface molecules that guide regenerating fibers. In most cases Physiopedia articles are a secondary source and so should not be used as references. "Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres." Gaudet AD, PopovichPG &Ramer MS. Wallerian degeneration: Gaining perspective on inflammatory events after peripheral nerve injury.Journal of Neuroinflammation.2011 Available from. Available from. Finally, the entire nerve is wrapped in a layer of connective tissue called theepineurium.[1]. These factors together create a favorable environment for axonal growth and regeneration. The prognosis, in general, is more favorable for a demyelinating lesion than for a lesion producing axonal loss. Wallerian degeneration is the process of antegrade degeneration of the axons and their accompanying myelin sheaths following proximal axonal or neuronal cell body lesions. Benefits: affordable, readily available, low risk of toxicity, Limitations: not been tested in mixed nerves, motor nerves, or jagged injuries, Acute, brief, low-frequency electric stimulation following post-operative peripheral nerve repair has been shown in human models to improve motor and sensory re-innervation. Possibles implications of the SARM1 pathway in regard to human health may be found in animal models which exhibit traumatic brain injury, as mice which contain Sarm1 deletions in addition to WldS show decreased axonal damage following injury. NCS: Loss of NCS waveforms below the lesion once distal axon degeneration (Wallerian degeneration) is complete. Axonal regeneration is faster in the beginning and becomes slower as it reaches the nerve end. The symptoms take effect immediately, but it takes 21 days for acute denervation changes to develop on needle EMG. E and F: 42 hours post cut. Degeneration usually proceeds proximally up one to several nodes of Ranvier. The type of surgery can be guided by the size of the gap of injury: Autologous graft to provide a conduit for axonal regrowth. This further hinders chances for regeneration and reinnervation. Traumatic injury to peripheral nerves results in the loss of neural functions. Physiopedia articles are best used to find the original sources of information (see the references list at the bottom of the article). R. Soc. Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. This page was last edited on 30 January 2023, at 02:58. Affected axons may . Macrophages are facilitated by opsonins, which label debris for removal. Wallerian degeneration is the catabolic process of degeneration of a neuron or axon that occurs without influencing the main cellular body and without the affected neuron actually dying . [31] This in turn activates SIRT1-dependent process within the nucleus, causing changes in gene transcription. endstream
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. If the axons fail to cross over the injury site, the distal segment is permanently denervated and the axonal growth from the proximal segment forms a neuroma. Possible effects of this late onset are weaker regenerative abilities in the mice. For example, bilateral cerebral infarction can produce atrophy of the intervening corpus callosum due to Wallerian degeneration of the commissural fibers. {"url":"/signup-modal-props.json?lang=us"}, St-Amant M, Smith D, Baba Y, et al. Nerves are honeycomb in appearance and mild hyperintense at baseline. (2005)[15] observed that non-myelinated or myelinated Schwann cells in contact with an injured [21] Grafts may also be needed to allow for appropriate reinnervation. For instance, the less severe injuries (i.e. The 2023 edition of ICD-10-CM G31.9 became effective on October 1, 2022. | Find, read and cite all the research you . Wallerian degeneration is an active process of retrograde degeneration of the distal end of an axon that is a result of a nerve lesion. Peripheral nerve repair with cultured schwann cells: getting closer to the clinics. !/$vhwf,cliHx$~gM])BP(Reu[BG4V`URV.//] L7o}%.^xP]-0n'^5w7U?YO}U[QtPog7fj(HY7q Schwann cells have been observed to recruit macrophages by release of cytokines and chemokines after sensing of axonal injury. Neuregulins are believed to be responsible for the rapid activation. Peripheral neurological recovery and regeneration. The pathological process of Wallerian degeneration is in 3 stages; Within approximately 30 minutes of injury, there is a separation of the proximal and distal ends of the nerve. Rehabilitation is directed toward improving or compensating for weakness and maintaining independent function. Peripheral nerve injury: principles for repair and regeneration.