Adhesive arachnoiditis (AA) is a progressive, inflammatory disease that causes painful scarring of the spinal cord and impedes nerve conduction and the flow of spinal fluid. Its increasing prevalence demands that pain practitioners recognize the condition and properly treat it. Without prompt management, AA causes severe debility and suffering among patients. The first part of this 2-part series reviewed the clinical description of AA.¹
Part 2 will present 4 patients with magnetic resonance image (MRI)-documented cases of AA. These cases were selected because they have slightly different initiating causes and treatments. All have been able to improve pain relief, function, and quality of life with treatment. AA patients will almost always demand an aggressive multi-faceted treatment approach with standard measures, as well as some off-label and non-standard measures. In many ways, AA patients are the prototype of the most severe, intractable pain patients, as they will inevitably require a multiplicity of treatment measures including opioids.
If a clinician reads any publication about AA, they will find that there is no known cure and that the aim of treatment is to alleviate pain and other symptoms such as urinary retention, impotence, and hypertension.²The National Institute of Neurological Disorders and Stroke recommend “a regimen of pain management, physiotherapy, exercise, and psychotherapy.” AA patients can be harmed if a practitioner is not aware of some hazards.
Case 1: Post-Lumbar Surgery
A man in his 40’s developed chronic back pain after lifting boxes. In 1999 at the age 46, he underwent a microdiscectomy at L4/L5. The attending surgeon placed 80 mg of methylprednisolone in the surgical area prior to completion of the surgical procedure. Shortly after the surgery, the patient developed severe pain and was diagnosed with AA by MRI. The cause of the AA was likely the placement of a corticosteroid directly into the surgical site.
To relieve the patient’s pain, he was started on a regimen of opioid drugs. Over the ensuing years, the patient saw numerous physicians and underwent a number of procedures, including nerve blocks and electromagnetic measures, as well as trials of numerous medications. Despite these interventions, he progressively worsened over time and was referred to our intractable pain program in March 2007.
When he presented to our clinic, the patient’s pain was grossly uncontrolled. The patient’s pain management regimen included: (1) fentanyl transdermal patch, 100 mcg every other day; (2) transmucosal fentanyl, 800 mcg 8 times per day; and (3) duloxetine (Cymbalta) 60 mg per day.
At the time of referral, the patient was in agony and could not stand for more than 5 to 10 minutes. He spent most of his initial evaluation lying on the clinic floor. He described his pain as being from the waist down and that it was an intense, burning sensation. Walking, standing, or movement made it worse. Most of each day he was bed-bound.
Our initial clinical treatment consisted of adding the following to his analgesic regimen: (1) acetazolamide (Diamox) 500 mg daily, which is approved to treat glaucoma, to lower pressure within the spinal cord; (2) hydromorphone 8 mg every 4-6 hours for breakthrough pain; and (3) topical morphine massaged over the site of his adhesions. He was taught gentle stretching exercises of both extremities and lumbar spine.
Since his first visit in 2007, he has progressively improved and does not need to lie down to find pain relief. Beginning in 2010, he progressively began to lower his opioid dosage to the point that he is now on the following opioids: oxycodone immediate release, 60 mg per day; and hydromorphone, 48 mg per day. He believes he can eventually be taken off his opioids as he now has some pain free hours.
In 2013, the patient’s serum testosterone level was tested for the first time and was found to be low. He was placed on human chorionic gonadotropin (HCG) 250 units per day. Today, his testosterone level is normal. He routinely uses inversion stretching by hanging upside down. A repeat MRI showed only epidural fibrosis. He has returned, part-time, to his business of selling auto parts, and he credits most of his current steady improvement to HCG and inversion stretching.
Case 2: Trauma and Electrocution
In 1998, a then 28-year-old man fell 30 feet from an overhead crane and became entangled in electric wires, where he was electrocuted with 440 watts of electricity. An MRI performed shortly after the fall showed clumping of the nerve rootlets of the cauda equina at the L-3 level. The diagnostic imaging also showed degenerative changes in the cervical and lumbar spines. The patient was diagnosed with AA and was begun on opioid medications for pain relief. He has been on opioids for more than 15 years.
The patient was referred to our clinic in 2011, when he was 51. At the time of referral his medication regimen included oxycodone extended release, 80 mg 9 times per day—total daily dose: 720 mg; hydromorphone immediate release, 80 mg per day; and fentanyl transmucosal, 1600 mcg twice daily. Despite this regimen, the patient was bed-bound most days and experienced increased pain with walking, lifting, sex, bending over, and lying down for more than 2 hours.
The patient was taught gentle stretching exercises of the extremities and spine, and was started on morphine extended release, 100 mg 3 times per day, and his fentanyl transmucosal dose was increased to 3 times per day. This regimen has remained stable since 2011, and he is no longer confined to bed, can drive a car, and is able to carry on all activities of daily living.
Today, at age 54, the patient’s opioid regimen consists of: (1) oxycodone extended release, 80 mg 9 time a day; (2) transmucosal fentanyl, 1600 mcg 3 times per day; (3) morphine extended release, 100 mg 3 times per day; and (4) hydromorphone immediate release, 8 mg, taken 3 to 4 times a day for breakthrough pain.
The patient describes his pain as severe and constant. Without his current opioid regimen, the patient is unable to function or get out of bed. A possible contributor to his need for a high-dose opioid regimen is that he has 2 cytochrome P450 defects (2C9 and 2C19) and ulcerative colitis. Ulcerative colitis is, itself, a painful, autoimmune disorder that may require analgesic relief. Opioid serum levels were obtained to determine if his opioids were therapeutically effective: (1) oxycodone 270 ng/mL; (2) hydromorphone 9.2 ng/mL; and (3) fentanyl 1.0 ng/mL. He has remained on essentially the same opioid regimen for more than 5 years.
The patient attends the clinic in an ambulatory, alert state. His vital signs are always within the normal range, with a normal size, reactive pupil. His most recent blood pressure was 136/91 mm/Hg and pulse rate was 92 beats per minute. His ancillary medications include: (1) temazepam (Restoril), 30 mg for insomnia; and (2) topical carisoprodol at a dosage of 350 mg and prednisone 10 mg in one ounce of cold cream base, which is massaged over his adhesive site.
Dietary supplements include vitamin D, fish oil, calcium, and coconut oil. His hormone serum levels are normal. He performs stretching exercises almost every day. His full upward arm reach has increased from about a 70% reduction to almost full range. He has no urinary or bowel dysfunction and considers himself lucky to be alive, functional, and have an acceptable quality of life.
Case 3: Post-Lumbar Surgery and Epidural Injections
A 51-year-old woman developed lumbar discogenic pain, although there was no known initiating event. A lumbar discogram caused an increase in her pain most likely due to increased pressure in the disc. Over the next 6 months she developed progressive radiculopathy, and she underwent an L4-L5 microdiskectomy procedure. After the surgery, she felt much better for a few weeks, but her pain returned. She then had an epidural corticosteroid injection, which made her pain unbearable. An MRI showed “considerable abnormal clumping of the cauda equina nerve rootlets throughout the lumbar spine, greater in the lower lumbar thecal sac.”
After her diagnosis of AA she was started on opioids but her pain was not well controlled. When she was referred to our clinic, she was on a treatment regimen that included: (1) oxycodone extended release, 40 mg 3 times per day; (2) hydromorphone, 32 mg per day; (3) alprazolam, l.75 mg per day; and (4) gabapentin, 300 mg per day. She has remained on this regimen.
On the above regimen, she described her pain as “extremely sharp, electrical, and intense.” It was constant, and she had severe insomnia. Standing or walking increased her pain. She had constipation and urinary hesitancy. Despite her high-dose opioid regimen, she was confined to home and bed.
Our examination included blood work, including a complete hormone profile. The patient’s hormone profile showed some severe hormonal deficiencies: (1) cortisol 1.2 mcg/dL (normal 4.0-20); (2) testosterone <3 ng/dL (normal 3-41); (3) dehydroepiandrosterone (DHEA) 0.158 ng/dL (normal 0.630-4.7); (4) pregnenolone 12 ng/dL (normal 15-132). In addition, her C-reactive protein was 5.9 mg/L (normal 1-5.0).
The first step in treatment was to replace the hormones that were low by administration of the following: (1) hydrocortisone, 15 mg per day; (2) DHEA, 200 mg per day; (3) pregnenolone, 50 mg per day; and (4) HCG, 250 units per day to raise testosterone and DHEA levels.
She was also started on acetazolamide 250 mg per day. Her pain improved by 40% to 60% within 10 days, and she could begin walking and leaving her home. The glial cell suppressor, minocycline, and the anti-infectious, anti-inflammatory agent, metronidazole, was added to her regimen. She has been taught stretching of the upper and lower extremities and lumbar spine. She applies topical lidocaine and prednisone to a recurrent, inflamed area on the lower left quadrant of her back.
Today, she can walk without exacerbating her pain. Her hormone levels and C-reactive protein have returned to normal. She believes her pain is reduced about 50%, and she is no longer house or bed-bound.
Case 4: Post Trauma and Excessive Corticosteroid Injections
A 39-year-old male who weighs 350 pounds had a broadside auto accident in 1994 at age 19. He sustained a L1 compression fracture, which at the time was not surgically treated. After the accident, the patient developed constant back pain, which radiated down his right lower extremity. An MRI in 1996 showed multiple bulging lumbar discs but no arachnoiditis. The patient was prescribed low-dose opioids but he progressively worsened.
In an attempt to relieve his symptoms, the patient underwent a series of 3 epidural corticosteroid injections in the year 2000. Methylprednisolone was the agent used. After the procedures, the pain persisted and multiple physicians, including 3 pain specialists and 3 university pain clinics, saw the patient. By his count, over the subsequent 8-year period, he was given over 40 additional corticosteroid nerve blocks, facet joint injections, epidurals, and trigger point needles into his lumbar spine area.
For the last 10 years, he has been unable to work and has been declared disabled. His pain progressively worsened and he was unable to stand longer than 10 minutes. His physicians progressively increased his opioid dosage.
An MRI in 2014 revealed clumping of the cauda equina nerve roots at the L5 level. Consequently, he was referred to our clinic for management of AA. At the time of referral, his medication regimen included: (1) oxycodone extended release, 12, 80 mg tablets per day—total dose: 960 mg/d; (2) hydromorphone, 48 mg per day; (3) gabapentin, 900 mg per day; and (4) tramadol, 200 mg per day. The patient believed the weak opioid tramadol aided his relief. He was also taking testosterone replacement to treat hypogonadism. This regimen was kept in place while other measures were added.
Hormone and inflammatory marker profiles were normal except for serum progesterone, which was at trace level. Corticotropin, cortisol, testosterone, DHEA, and pregnenolone were normal. His treatment regimen has been expanded to include: (1) stretching exercises; (2) acetazolamide, 250 to 500 mg per day; (3) minocycline, 300 mg per day; (4) methadone, 10 mg 3 times per day; and (5) topical progesterone.
The initial treatment goal was better pain relief, more mobility, and decreased oxycodone usage. After about 2 months, the patient claims he has more mobility, less pain, and increased sleep and energy. His treatment will likely last a lifetime, so his outcome is somewhat unpredictable.
Notes On Some Treatment Measures
Adhesive arachnoiditis may produce a pain severity that is profound. I have included a few “dos” as well as “dont’s” (Table 1). The patients reported here all required high opioid dosages to be able to escape an immobile, debilitated state. A common theme among AA cases I’ve seen, is that movement causes intense pain unless opioid therapy is adequate. The use of acetazolamide, which is a carbonic anhydrase inhibitor, is theorized to reduce spinal fluid pressure similar to its glaucoma effect. Aldrete initially recommended this agent for AA.² Spinal flow may back up and be impeded by adhesions. This pathologic situation may cause fluid pressure and acetazolamide may provide relief. An increase in spinal pressure above an adhesive area that impedes flow of spinal fluid may be a cause of headache, pain, and weakness of the lower extremities. It is also possible that standing further constricts the blocked area, and it provides a positive explanation as to why lying on the floor relieves pain since spinal fluid can pass through the adhesive area. Patients here, at least on a temporary basis, seemed to have some symptom relief with acetazolamide. It may also affect neuropathic pain by a mechanism other than reducing fluid pressure.³
Minocycline is known to suppress glial cell activity, which attenuates neuropathic pain.⁴˒⁵ Metronidazole has anti-inflammatory activity as it is used to treat rosacea and inflammatory bowel disease.⁶ The third case presented here was given metronidazole for a urinary tract infection, and it greatly relieved her AA pain. When she stopped metronidazole, her AA pain flared. Consequently, she was allowed to remain on this agent.
The cases reported here, as well as others I have treated, respond to gentle stretching exercises of the extremities and spine. The idea is to stretch the spinal cord to allow better passage of spinal fluid, break up adhesions, and hopefully produce some normal nerve root growth and function. I also recommend trampoline walking to increase lymphatic-spinal fluid flow and inversion stretching on an inversion table.
An AA patient should not be treated by any physical therapist unfamiliar with AA. Massage, stretching, or manipulation can seriously hurt the AA patient, since the pain site is scarred with adhesions. Too vigorous manipulation may cause a tear, intense pain, and permanently aggravate the existing pathologic condition.
I do not recommend any injections of any kind be done in or around the adhesive site. AA is a progressive, inflammatory condition, so I am leery of any needle-based procedure near or around the adhesive site lest a well-intended effort make the condition worse. Any needle injection will produce some inflammation, so I advise against the use of all needle injections near the site. Therapeutic needle-based injections include trigger points, acupuncture, homeopathy, and prolotherapy. Basically, my recommendation is to let the AA site benefit from stretching, nutrition, hormones, and analgesia.
The AA patients I have seen appear to have some allergic or autoimmune sensitivity to some foods and drugs. I start all therapeutic, nutritional, and hormonal agents at low dosages and titrate upward over time. For example, the second patient presented here has attempted several ancillary agents such as hormones and muscle relaxants, but could not tolerate them as they produced dysphoria, dizziness, and increased pain.
HCG was used in 2 of the 4 cases, and both patients believe it was greatly responsible for their positive progress. HCG is labeled for hypogonadism, and it will raise estrogen, testosterone, and progesterone serum levels.⁷It also has the innate, natural function of neurogenesis. For example, in the embryo it is responsible for the growth of ectoderm, hair, nails, skin, and nerves. Hopefully HCG causes some neurogenic activity in the adhesive site.
Discussion
Adhesive arachnoidistis is a prototype for severe intractable pain patients such as the ones referred to my practice. My referral practice has dramatically changed over the past decade, in that patients seen today come with a much more complicated history, having seen numerous physicians and already on a multi-medication-opioid regimen. Quite frankly, I can’t remember the last time I initiated opioid therapy, as it was several years ago. I recently reviewed 40 consecutive referral cases to my clinic. These 40 patients had seen 450 physicians, 185 pain specialists, 103 psychiatrists or psychologists, and been evaluated at 23 universities. They were referred with a medication history, on average, of more than 11 medications including 2 to 3 opioids each. The AA patients described here were typical of my practice, in that they were on multiple opioids and had all seen numerous physicians, pain specialists, and been evaluated at universities but were not doing well.
My approach is to leave in place, to the extent possible, the existing treatment program and add to it. In the case of opioids, it is standard practice to add a long-acting opioid when a short-acting opioid is not adequate. When patients such as the cases reported here are referred to me, they may have an opioid regimen that has evolved through many well-intended physicians who were diligently trying to provide an effective regimen. Consequently, the normal standard of a long-acting opioid with a short-acting opioid prescribed for breakthrough pain is long gone. In general, I try to avoid long-acting opioids or raising the dosage of one due to endocrine suppression. It is clear that about 75% to 85% of patients on long-acting opioids, including intrathecal routes, will exhibit endocrine suppression.⁸⁻¹⁰ If a patient is disciplined and intelligent, he/she may be prescribed multiple short-acting opioids to provide adequate pain relief, while allowing the serum level of the opioid to drop to a low enough level in a 24 hours period to allow the hypothalamus and pituitary to avoid opioid suppression.
On the other hand, severe pain such as seen in AA may require multiple long-acting opioids, which will almost always require some hormone replacement. In summary, severe, intractable pain patients can’t be put in a “one-way” treatment box. Their opioid regimen will have to be tailored individually and revised over time, particularly as the clinical situation and financial capability of the patient may dictate.
Therapeutic blood monitoring of opioids can contribute to clinical decision making in a severe, intractable pain patient. The major clinical point to be determined by an opioid blood level is whether it is present in an adequate concentration to be effective. If a patient is being prescribed a high opioid dosage, a serum opioid concentration over about 10 to 20 ng/mL for most opioids at the same time as the patient is ambulatory, alert, and has normal vital signs indicates that the patient is doing well and can carry out activities of daily living, including driving. A patient who has a low opioid blood level may not be getting adequate analgesia due to gastrointestinal malabsorption and/or a genetic metabolic defect. Just as with urine drug testing, the presence of opioids in the blood cannot tell you if 100% of an opioid dosage has been taken.
The newest element in intractable pain management is that almost all pain patients with constant, debilitating pain have centralized pain. Centralization is usually accompanied by a peripheral neuropathic condition. Neuroinflammation is the underlying problem in centralized pain, and it is due to microglial activation. Two new classes of drugs are now being identified and investigated: glial cell suppressors and neurohormones. It is far too early to make any strong clinical claims, but I am personally quite encouraged. These hormones are produced inside the central nervous system and all have neurogenic properties: progesterone, estrogen, HCG, oxytocin, and pregnenolone.¹¹˒¹² Today I try to raise serum levels of testosterone, estrogen, and progesterone with HCG, in males and females, on the theory that I may get both a hormone and neurogenic effect. It doesn’t always work, so testosterone, progesterone, or estrogen may have to be replaced. The realization that severe pain may be centralized with sensitization and neuropathic concomitants is allowing us to proceed in a most positive direction to hopefully better help the severe suffering, intractable pain patient like those with AA.
Summary
Adhesive arachnoiditis is an inflammatory process with peripheral and central components. There is no reported treatment except symptomatic pain relief for AA, and it is believed to be incurable.² Some of the cases reported here, however, appear to have greatly improved. Some of my therapeutic dos and don’ts are cited in Table 1. Hopefully you find some useful tips.
Keep in mind that the pain severity of AA will usually require high-dose opioid therapy to make the patient comfortable long enough to begin stretching exercises, which in my experience are essential in AA. The cases reported here are primarily intended to illustrate the point that aggressive treatment including some off-label, non-standard measures will provide some humane care. My clinical experience indicates that the outcome of AA can be better than generally suggested in the literature.