Epidural injections of indomethacin for postlaminectomy syndrome: a preliminary report. This leads to a condition called chronic adhesive arachnoiditis. His MRI has revealed clumping of the Cauda Equina consistent with Arachnoiditis. Although arachnoiditis can be present throughout the subarachnoid space, it is most easily seen in the lumbar region where the cauda equina usually floats in ample CSF. In: Frontera WR, Silver JK, Rizzo TD, eds. Cauda equina syndrome. Xle I, Kang H, Xu Q, et al. {"url":"/signup-modal-props.json?lang=us"}, Radswiki T, Baba Y, Saber M, et al. That is generally from a degenerative disc or facet. Loss of bladder and bowel control can be extremely distressing and have a highly negative impact on social life, work and relationships. Join a support group for chronic pain and/or arachnoiditis to learn from other people with similar conditions. They send and receive messages to and from your legs, feet, and pelvic organs. Despite the lubricating properties of spinal fluid, spine deformities and imbalances produced by scoliosis, cysts, or arthritis may cause enough compression and friction between nerve roots to cause irritation, activation of glia cells, and neuroinflammation. Symptoms Although early treatment is required to prevent permanent problems, cauda equina syndrome may be difficult to diagnose. The conus is normal in appearance and terminates at the T12 level. A number of case reports have shown linked arachnoiditis in the pathogenesis of the cauda equina syndrome of ankylosing spondylitis. As far as I can determine, the term chronic cauda equine syndrome is not due to nerve root compression but, rather, neuroinflammation of the nerve roots in the cauda equinein effect, it may be considered an alternate name for AA. Singh R, Sen I, Wig J, Minz M, Sharma A, Bala I. Shaw MD, Russel JA, Grossart KW. The cauda equina is the conglomeration of the nerve roots of the lumbar and sacral spinal nerves . It is best if this occurs within 48 hours of the onset of symptoms. Straight leg raising and foot flexing will put some stretch on nerve roots. Patients with CES may develop frequent urinary infections. Wilmink. Kumar A, Montanero W, Wilinsky R, TerBrugge KG, Aggarwal S. MR features of tubercular arachnoiditis. I would love to hear from you on your opinion,if any. Check for errors and try again. In patients with cauda equina syndrome, something compresses on the spinal nerve roots. Her MRI (Figure 5, C) is still abnormal. Tests that May be Helpful in Diagnosing CES. You may be asked to stand, sit, walk on your heels and toes, bend forward, backward and to the sides, and lift your legs while lying down. Viewing 2 posts - 1 through 2 (of 2 total). Arachnoiditis is usually chronic (lifelong) and may be progressive, meaning it gets worse over time. !he read all of my issue and details and his replies really helped me in decidingi am now confident about my decision and i now totally understand the procedure thanks to the in-depth information providedthank you ever so much ! Case study, Radiopaedia.org (Accessed on 02 May 2023) https://doi.org/10.53347/rID-33345. Treating patients within 48 hours after the onset of the syndrome provides a significant advantage in improving sensory and motor deficits as well as urinary and rectal function. Arachnoiditis has traditionally been considered a rare, hopeless disease, but it is now emerging as relatively common entity that can be treated. OCallaghan JP, Sriram K, Miller DB. Delamarter RB, Ross JS, Masaryk TJ, Modic MT, Bohlman HH. Emergency Radiology. The conus medullaris forms the last portion of the spinal cord from where the axons of the distal nerve roots originate and where the spinal bowel and bladder centers are located. Cauda equina syndrome occurs when the nerve roots in the lumbar spine are compressed, cutting off sensation and movement. Mid-sagittal T2-weighted view demonstrating absence of compressive lesion but showing clumping of the cauda equina nerve roots resulting in a 'pseudo-cord' appearance (black arrows). The effects of minocycline or riluzole treatment on spinal root avulsion-induced pain in adult rate. Cauda equina syndrome results from compression (squeezing) of the cauda equina-the sac of nerves and nerve roots at the base and just below the spinal cord in the lumbosacral spinal canal. Retained surgical swab debris in postlaminectomy arachnoiditis and peridural fibrosis. Pain in the back and/or legs (also known as sciatica). Los Angeles Times Versus Purdue Pharma: Is 12-Hour Dosing of OxyContin Appropriate? Exercises are essential to prevent spinal nerve roots from clumping, scarring, and forming adhesions that can lead to lower extremity paraparesis and/or paralysis. Gently bouncing on a trampoline or rocking in a chair provides comfort and hopefully increases spinal fluid flow. Adding lumbar spine MRI to the current . People with cauda equina syndrome often are admitted to a hospital as a medical emergency. 7. Arachnoiditis can cause many symptoms, including: Symptoms may become more severe or even permanent if the condition progresses. Inflammation begins in cauda equina nerve roots leads to Adhesions causing clumping of nerve roots CONCLUSIONS: 1. Lefaix JL, Delanian S, Vozenin MC, Leplat JJ, Tricaud Y, Martin M. Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: an experimental study. It can cause severe pain and neurological symptoms, such as muscle weakness. She will be followed indefinitely. Raghavendra V, Tanga FY, DeLeo JA. Besides a herniated disc, other conditions with symptoms that can be similar to CES include peripheral nerve disorder, conus medullaris syndrome, spinal cord compression and irritation or compression of the nerves after they exit the spinal column and travel through the pelvis a condition known as lumbosacral plexopathy. This may relate to any interval spinal intervention, infection or trauma . Gitelman A, Hishmeh S, Morelli B et al. Nerve damage and possibly tethered nerves. Kunam VK, Velayudhan V, Chaudhry ZA et-al. Could late dx of Hirschsprungs Disease account for the perceived neuropathy. Become a Gold Supporter and see no third-party ads. Avidan A, Gomori M, Davidson E. Nerve root inflammation demonstrated by magnetic resonance imaging in a patient with transient neurologic symptoms after intrathecal injection of lidocaine. Cauda equina syndrome (CES) occurs when there is dysfunction of multiple lumbar and sacral nerve roots of the cauda equina. Degenerated arthritic joints, trauma, or scoliosis that cause friction or compression between some of the nerve roots also may cause AA. Having depression or anxiety can make your chronic pain worse. Today, the practice follows about 65 cases. Myeloscopy is the procedure by the fluid filled space within the water jacket (dura) is explored with the patient in the aware state and able to attest to the presence of pain or symptoms, This reveals that such clumping is rare and is only symptomatic when the adjacent Dura is inflamed. While there are therapies and treatments that can help manage symptoms, theres no cure. The anatomy of the cauda equina on CT scans and MRI. The features are characteristic of arachnoiditis, which is secondary to a wide number of insults. Get useful, helpful and relevant health + wellness information. If you have any of these symptoms, see your doctor right away: A doctor can diagnose cauda equina syndrome. Benner B, Ehni G. Spinal arachnoiditis: the post-operative variety in particular. Drink plenty of fluids and practice regular personal hygiene to prevent urinary tract infection. L3/4: Asymmetric disc bulge with minor central canal and left subarticular recess narrowing. Vale ML, Benevides VM, Sachs D, et al. Urinary retention: the most common symptom. For example, some patients may show clumping with few or no clinical symptoms while others may have severe symptoms with questionable or marginal clumping. Arachnoiditis causes severe stinging, burning pain and neurological problems. Your cauda equina syndrome is chronic. -. Space-occupying lesions, including disc herniation, trauma and tumor, within the spinal canal may compromise the nerve roots, causing severe clinical syndromes. Impaired blood supply to the affected nerves. 11. Arachnoiditis may acutely appear after a single spinal tap, epidural anesthesia, epidural corticosteroid injection, surgery, trauma, or viral infection. Recent studies show that the frequency of lumbar arachnoiditis appears to be increasing due to an increasing amount of lumbar spine surgeries. Nerve severance is a permanent loss. Cauda equina syndrome can present either acutely or chronically and requires two sets of symptoms/signs 1-3: perianal and "saddle" paresthesia. J Craniovertebr Junction Spine. Conclusions: Cauda equina nerve root thickening is associated with Krabbe disease in both treated and untreated patients. Periodic assessment of renal function is essential with ketorolac administration, and it will have to be discontinued if renal function is adversely affected as indicated by elevated levels of creatinine or blood urea nitrogen, or reduced glomerular filtration rate. Even with treatment, you may not retrieve full function. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Lavy C, James A, Wilson-MacDonald J, Fairbank J. Cauda Equina Syndrome. Normally nerve roots of cauda equina should fall freely in the dependent portions of thecal sac appreciated most easily against the background of high signal intensity Csf on Axial T2 images. 1990;53(12):1076-9. 2016;16(5). Depending on the cause of your CES, you may also need high doses of corticosteroids. The diagnosis of AA is made by history, physical, and a confirmatory MRI. The message is simple, keep exercising or become paralyzed. In addition, some patients find that physical therapy and psychological counseling help them cope with CES. He is in violent pain. 2018;38(4):1201-22. Policy. The patient has some residual, intermittent pain and her ability to perform straight leg raises still shows minor impairment. (2009) ISBN: 9783540938293 -. Grande L, Delacrue H, Thompson G, et al. At the time the article was created The Radswiki had no recorded disclosures. Medical protocols for acute and chronic AA have been developed and are published here for utilization in ambulatory care settings. Nerve damage and possibly tethered nerves. Cserr HF, Harling-Berg CJ, Knopf PM. ADVERTISEMENT: Radiopaedia is free thanks to our supporters and advertisers. 2. In patients with cauda equina syndrome, something compresses on the spinal nerve roots. . {"url":"/signup-modal-props.json?lang=us"}, Gaillard F, Arachnoiditis. You must be logged in to reply to this topic. In some individuals, CSF flow is impaired,and they may develop hydromyeliawhich should, therefore, be sought in the cord. Patients who are labeled failed back surgery syndrome undoubtedly have a very high prevalence of AA. Many persons with intraspinal canal inflammation develop the symptom profile of AA, but the diagnostic clumping of nerve roots which is necessary for a diagnosis of AA may not be evident. This type of pain tends to produce a burning feeling that can become constant and unbearable. Mayil S. Krishnam, John Curtis. Check for errors and try again. Maybe not. Spinal arachnoiditis: disease or coincidence? Reference article, Radiopaedia.org (Accessed on 02 May 2023) https://doi.org/10.53347/rID-12614. Imaging in Cauda Equina Syndrome--A Pictorial Review. Patients may not be able to do straight leg raises or flex one or both feet. Once the diagnosis of CES is made and the etiology established, urgent/emergent surgery is usually the treatment of choice. About OrthoInfoEditorial Board Our ContributorsOur Subspecialty Partners Contact Us, Privacy PolicyTerms & Conditions Linking Policy AAOS Newsroom Find an FAAOS Surgeon. Tennant F. Erythrocyte sedimentation rate and C-reactive protein: old but useful biomarkers for pain treatment. 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event, (https://rarediseases.info.nih.gov/diseases/5839/arachnoiditis), (https://www.ninds.nih.gov/health-information/disorders/arachnoiditis), (https://www.ncbi.nlm.nih.gov/books/NBK555973/). An MRI showed arachnoiditis and she was referred to my clinic. Defining neuroinflammation.. Additionally, cauda equina syndrome can be classified as incomplete or complete based on the presence of bowel and bladder symptoms 1,2,10: may have loss of urgency or decreased urinary sensation without incontinence or retention, accounts for ~40% (range 30-50%) of presentations 6, urinary and/or bowel retention or incontinence. Miserable quality of life. Nerve root clumping occurred in association with pure spinal stenosis . Some severe patients literally have so much pain, fatigue, and disability that they report to me that they spend 80% to 90% of their time in bed. These nerves send and receive messages to and from the lower limbs and pelvic organs. The course of this condition remains highly variable since arachnoiditis can be either a static (stays the same) or progressive (gets worse over time) disease. Considering that AA patients have constant pain and intermittent flares suggests that patients continually carry both neuroinflammatory and neuropathic components to their pain. 10. For example, if you have depression, the fatigue, sleep changes and decreased activity may worsen your chronic pain. Cauda equina syndrome may be caused by a herniated disk, tumor, infection, fracture, or narrowing of the spinal canal. Urinary and/or fecal incontinence. Haughton VM, Eldveik OP, Ho KC, Larson SJ, Unger GF. The progression may go up or down the spine. Nerve root or cauda equina inflammation can often be, however, observed on an MRI since inflammation causes edema (swelling), displacement, and the adherence or clumping of nerve roots to each other. Cauda equina syndrome can present either acutely or chronically and requires two sets of symptoms/signs 1-3: There is a host of associated symptoms and signs, which may be unilateral or bilateral and have a variable presence 1-3,6,10: radiculopathy/sciatica (unilateral or bilateral), paresthesia of lower limbs and perianal/saddle region (variable), weakness of lower limbs in a lower motor neuron pattern (variable). Causes of cauda equina syndrome include: trauma, spinal stenosis, herniated disks, Cauda equina syndrome is often treated using a surgical procedure called . 1987;149 (5): 1025-32. This may relate to any interval spinal intervention, infection or trauma during this period. Cleveland Clinic is a non-profit academic medical center. Approximately 20% of patients will have a poor outcome in terms of urological and/or sexual function, as well as lower limb paresthesia and weakness 6. CES occurs more often in adults than in children. The presence of an elevated ESR or CRP suggests, however, that AA is active and in need of treatment.. endstream endobj startxref Unable to process the form. Severe or progressive problems in the lower extremities, including loss of or altered sensation between the legs, over the buttocks, the inner thighs and back of the legs (saddle area), and feet/heels. Since the presentation of arachnoiditis ranges from very mild to severe, many mild cases of arachnoiditis will either never be diagnosed or arent reported. Although short-term recovery of bladder function may lag behind reversal of lower extremity motor deficits, the function may continue to improve years after surgery. Causes Cauda equina syndrome may be caused by a herniated disk, tumor, infection, fracture, or narrowing of the spinal canal. Tab will move on to the next part of the site rather than go through menu items. This inflammation produces adhesions that merge or "glue" these two separate anatomic structures together into an inflammatory-adhesive mass inside the spinal canal. Pain practitioners need to be aware of this possibility and be prepared to provide emergency treatment to prevent severe disability and impairment. Oral ketamine for chronic pain: a 32-subject placebo-controlled trial in patients on chronic opioids. hbbd```b``"d%duu@`%HX His bladder, bowel and sexual function is all now affected. Graeber MB. Many people with arachnoiditis are unable to work and have a significant disability because of constant pain. Drago F, Caccamo G, Continella G, Scapagnini U. Amphetamine-induced analgesia does not involve brain opioids. Once inflammation involves some of the nerve roots, it clinically appears to be capable of spread as AA patients recurrently claim that they may worsen following additional trauma, medical procedures (including physical manipulation and paraspinal injections), and even infections. Walking outside the house each day is mandatory. After 9 months her gait appears normal. Nerve root irritation or inflammation diagnosed by magnetic resonance imaging. Water immersion is highly recommended, as it allows better stretching and pain relief. Some general recommendations for managing bladder and bowel dysfunction: AAOS does not endorse any treatments, procedures, products, or physicians referenced herein. Upper, Middle, and Low Back Pain Symptoms, Cauda Equina Syndrome: Symptoms, Treatment, Surgery, and More, A severe ruptured disk in the lumbar area (the most common cause), A complication from a severe lumbar spine injury such as a car crash, fall, gunshot, or stabbing, A birth defect such as an abnormal connection between, Pain, numbness, or weakness in one or both legs that causes you to stumble or have trouble getting up from a chair, Loss of or altered sensations in your legs, buttocks, inner thighs, backs of your legs, or feet that is severe or gets worse and worse;you may experience this as trouble feeling anything in the areas of your body that would sit in a saddle (called saddle anesthesia), Sexual dysfunction that has come on suddenly, A medical history, in which you answer questions about your health, symptoms, and activity, Magnetic resonance imaging (MRI) scan, which uses magnetic fields and computers to produce three-dimensional images of your spine, A myelogram -- an X-ray of the spinal canal after injection of contrast material -- which can pinpoint pressure on the spinal cord or nerves, A continence advisorand continence physiotherapists. In addition to adhesions and scarring, AA patients may develop some interference with spinal fluid flow. Whatever the mechanism, patients may develop periodic blurred vision and severe headaches due to increased fluid pressure. Mental impairment and deterioration relative to attention span, memory, logistical or abstract thinking, and even reading and writing may occur. The other two layers are the dura mater and pia mater. Left and right arrows move across top level links and expand / close menus in sub levels. In cases where opioids have not been needed, low-dose naltrexone (1 to 5 mg a day) has been effective in my hands. Eur Spine J. 2010;1 (2): 100-6. There is pressure on the nerves at the very bottom of the spinal cord. Is this possible or is there another form of treatment you can provide to arrest this beast? It affects millions of people. Be sure to seek out a healthcare provider whos familiar with arachnoiditis. Arachnoiditis may cause disability in some people, and they may be unable to work full time due to constant pain and various neurological issues. Some patients report that pain is so excruciating that high-dose opioids are required for even a modicum of pain control. Arachnoiditis is a broad term encompassing inflammation of the meningesand subarachnoid space. Empty the bladder completely with a catheter 3 to 4 times each day. Over the past 4-5 years he has developed severe back/leg pain. The symptoms can vary based on which part of your spine (which spinal nerve) is affected and can range from mild to severe. Aldrete JA. At this juncture the author has seen success with a number of pain control regimens and agents. Changing face of microglia. Clumping of the nerve roots is a new finding compared to scan from 5 years ago (not shown) and is consistent with arachnoiditis. At the time the case was submitted for publication Frank Gaillard had no recorded disclosures. Could this actually be the rare case of piriformis syndrome. Arachnoiditis is unusual to occur absent some injury or insult. Enter and space open menus and escape closes them as well. Acetazolamide and midazolam act synergistically to inhibit neuropathic pain. Pi R, Li W, Lee NT, et al. This regimen was developed, in part, by finding very low serum cortisol levels late in the day and evening in AA patients and the presence of inflammatory markers that did not decrease with most anti-inflammatory agents.. If needed, use. It is characterized by thickening of the arachnoid membrane and dura mater adhesions that result in chronic lower back pain. Spine_. The size of the disc herniation that results in cauda equina is often much larger than normal; however, if the spinal canal is smaller due to conditions such as arthritis, a smaller disc herniation can produce CES. Given this clinical observation, neuroprotection seems as equally important as is neurogenic efforts to repair and regrow damaged and inflamed nerve roots. They are primarily in the posterior portion of the thecal sac between L1 to L3 and then move forward or anterior (Figures 2 and 3). American Association of Neurological Surgeons: "Cauda Equina Syndrome (CES). Streit WJ, Mrak RE, Griffin WS. What is adhesive arachnoiditis? Although the term cauda equina syndrome has traditionally only referred to the acute compression of the nerve roots, some practitioners have used the term chronic cauda equina syndrome when bladder and bowel dysfunction, pain, and some paraparesis coexist. In addition, cauda equina syndrome is a rare but well-recognized complication of longstanding ankylosing spondylitis. Often, healthcare professionals recommend a program of the following: Unfortunately, theres no known way to prevent arachnoiditis. He or she will then assesses stability, sensation, strength, reflexes, alignment and motion. %PDF-1.5 % Up and Down arrows will open main level menus and toggle through sub tier links. CES can affect people both physically and emotionally, particularly if it is chronic. While its not life-threatening, the chronic pain and neurological issues associated with arachnoiditis can greatly affect your quality of life. As noted, the dual concepts of neuroprotection and neurogenesis are essential for the management of AA. Tennant F. Search for inflammatory markers in centralized, intractable pain. When cauda equina compression occurs, it is a neurosurgical emergency because the nerve roots must be released to prevent lower extremity paraparesis, paralysis, bladder and bowel impairment, and severe pain. Over the past 5 years, my clinic has admitted to treatment an increasing number of patients with AA. Rydevik B, Holm S, Brown MD, Lundborg G. Diffusion from the cerebrospinal fluid as a nutritional pathway for spinal nerve roots. Many of these patients also require long term follow-up with rehabilitation medicine. The arachnoid mater is the middle layer. Background: The lumbosacral intrathecal anatomy is complex because of the density of nerve roots in the cauda equina. Jeffrey Fudin, PharmD, FCCP, FASHP, FFSMB. Saddle anethesia sensory disturbance, which can involve the anus, genitals and buttock region. The pressure on the nerves stops the nerves from working properly. But in rare cases, severe back pain can be a sign of cauda equina syndrome (CES), a condition that usually requires urgent surgical treatment. It is worth remembering that cauda equina syndrome is a clinical diagnosis and thus the term should not be used in a radiology report unless the appropriate symptoms and signs are known. As a result of inflammation, the nerve roots become adherent to each other and to the theca. Sweitzer SM, Schubert P, DeLeo JA. %%EOF [3] Cauda equina syndrome occurs when the nerve roots in the lumbar spine are compressed, disrupting sensation and movement. Many people with arachnoiditis, however, can walk and drive a car without significant limitations. Topiramate in chronic lumbar radicular pain. If patients with cauda equina syndrome do not receive immediate, appropriate treatment to relieve the pressure, it can result in permanent paralysis, impaired bladder and/or bowel control, loss of sexual sensation, and other problems. Treatment options for arachnoiditis are similar to those for other chronic pain conditions. Due to these changes in the arachnoid and nerve roots, arachnoiditis frequently results in pain and possible neurological deficits, such as muscle weakness and sensory issues. Arachnoiditis most commonly affects the nerves connecting to your lower back and legs (lumbar spine). In my experience, 30% to 40% of AA patients demonstrate elevated erythrocyte sedimentation rates (ESR) or high sensitivity C-reactive protein (CRP) levels. CRP levels may be exceedingly high. Cauda equina syndrome (CES) is a particularly serious type of nerve root problem. Nevertheless, it is sometimes included under the broader meaning of arachnoiditis and certainly can mimic run-of-the-mill inflammatory arachnoiditis. Redundant nerve roots of the cauda equina are characterized by the presence of elongated tortuous nerve roots with serpiginous or coiled appearance near areas of spinal canal stenosis.. 2011;20(5):690-7. You will need to learn ways to adapt to changes in your body's functioning. Am J Orthop (Belle Mead NJ). 2013;82(2):100-8. All material on this website is protected by copyright. A significant number of AA patients have presented to my clinic with advanced disease. I have researched extensively but it appears nothing can be done, at least that is what every specialist has told us and we have seen just about every kind of specialist. hematogenous spread of systemic tumors (e.g. In this MRI scan, a herniated disk (arrow) is compressing the cauda equina. But it can occur in children who have a spinal birth defect or have had a spinal injury. 4. Cauda equina syndrome is a serious neurological emergency that can have devastating long-lasting neurologic consequences. Benoliel R, Tal M, Eliav E. Effects of topiramate on the chronic constriction injury model in the rat. Arachnoiditis from experimental myelograph with aqueous contrast media_. Technically, however, when adhesions to the arachnoid lining are not observed a more specific diagnosis might be cauda equina neuroinflammation.. Spinal stenosis was present in 44 patients giving an incidence of abnormal nerve root distribution of 36% in this group. Within a few hours after delivery of the baby, the patient developed severe lumbar back pain, headache, and great difficulty with ambulation. There are also no reliable laboratory tests or imaging test findings to definitively diagnose arachnoiditis. Coming to a Cleveland Clinic location?Hillcrest Cancer Center check-in changesCole Eye entrance closingVisitation and COVID-19 information, Notice of Intelligent Business Solutions data eventLearn more. Head, Arachnoiditis Research and Education Project, A Review of Skeletal Muscle Relaxants for Pain Management, Bench to Bedside: Clinical Tips from APS Poster Presentations. The cauda equina is the continuation of these nerve roots in the lumbar and sacral region. Even with immediate treatment, some patients may not recover complete function; earlier treatment does, however, offer thebest outcomes for cauda equina syndrome. Symptoms vary in intensity and may evolve slowly over time. Surgery must be done quickly to prevent permanent damage, such as paralysis of the legs, loss of bladder and bowel control, sexual function, or other problems. I ask, why cant the nerves be ablated at the start of the clump, remove the clump, to relieve the pain and the nerves allowed to flow freely as they regenerate? The nerve roots progressively exit the thecal sac beginning between L1 and L3. Check for the presence of waste regularly and clear the bowels with gloved hands. The patients bladder fills with urine, but the patient does not experience the normal sensation or urge to urinate. Inflamed nerve roots on an axial view appear as enlarged (edema), displaced from their normal position, and glued or clumped together (Figure 4). We teach patients to stretch both upper and lower extremities several times a day. Georges C, Lefaix JL, Delanian S. Case report: resolution of symptomatic epidural fibrosis following treatment with combined pentoxifylline-tocopherol.