Arachnoiditis is chronic inflammation of the arachnoid layer of the meninges which consists of trabeculae, a mesh of interwoven collagen fibrils resembling tissue paper. These secrete spinal fluid, which circulates through the cerebrospinal axis and is absorbed through the arachnoid villi in the brain.
The initial phase of the inflammatory process involves influx of white blood cells in response to an insult to the subarachnoid space, such as blood (trauma, surgery), foreign substance (dye, etc) or infectious agent (e.g. meningitis). This is initiated via the action of cytokines, (proteins that act as immune modulators). There is infiltration by macrophages and mesenchymal cells; the latter transform into fibroblasts, which make collagen (scar tissue).
Usually the fibrinolytic process, which breaks down excess scar tissue, limits this, but in arachnoiditis the scar tissue continues to form.
Authors such as Jayson have suggested that there may be a defect in the fibrinolytic pathway.
The neurosurgeon Mayfield, through his research in the 1980s, felt that there might be an immune response that is responsible for the degree of reaction, especially to chemical insult. Frank et al cultured arachnoidal cells in vitro and demonstrated their immune capabilities.
Anecdotal evidence suggests that a number of patients with arachnoiditis also have autoimmune type symptoms and/or a diagnosed coexisting autoimmune disorder such as Sjogren’s syndrome, Rheumatoid Arthritis, Systemic Lupus Erythematosus. These conditions are known to be associated with vasculitic neuropathies.
Also, Rheumatoid arthritis and various other connective tissue diseases show features of fibrosis
It therefore seems reasonable to hypothesise that arachnoiditis may be an autoimmune condition, possibly involving antibodies that affect the fibrinolytic pathway, such as anti plasminogen antibodies (seen in Rheumatoid Arthritis), in response to an insult to the arachnoid meninges, especially when that insult is chemical in nature.
There have been several papers recently discussing the possible role of previous viral infections, particularly Epstein-Barr virus (EBV) in the aetiology of autoimmune disorders such as Sjogren’s syndrome, and Systemic Lupus Erythomatosus. Many patients with arachnoiditis have had previous viral infections, including EBV and Cytomegalovirus (CMV). It is possible that this has some significance in the development of an autoimmune component to arachnoiditis, which could account for the degree of severity of the condition in that group of patients.
MacDonald noted that 18% of the general population carry a factor in the blood (Histamine Release Factor HRF) which causes a dramatically potentiated, sustained autoimmune reaction to foreign substance in the people who carry this factor. As this factor may be implicated in autoimmune responses, this may be relevant in explaining why there is only a minority of patients with arachnoiditis who develop the condition to a clinically significant degree.
PATHOLOGY
In the first stage the spinal nerves are
inflamed (radiculitis) and the adjacent blood vessels distended (hyperaemia). The subarachnoid space disappears. Deposition of collagen fibrils (scar tissue) begins. In thesecond stage, (arachnoiditis) the scar tissue
increases, and the nerves become adherent to each other and the dura. The third stage, (adhesive arachnoiditis), involves complete encapsulation of the nerve roots. The subsequent compression causes them to atrophy. The scarring prevents the arachnoid from producing spinal fluid in that area. These stages were described by Burton in 1978.
In some cases, the scar tissue calcifies (arachnoiditis ossificans).
Benini and Blanco described arachnoiditis as “cystic and adhesive in nature”. The cysts are collections of spinal fluid walled off by the meningeal adhesions. Arachnoid cysts are seen in some cases, especially if there is a foreign body present. They are particularly seen after Pantopaque myelography.
An animal study showed that there was proliferation of fibrous tissue, lymphocyte infiltration and that the pial blood vessels were obliterated. In the spinal cord adjacent, there were multiple small areas of demyelination. Cavitation of the cord was observed in areas where there was ischaemia (poor blood supply). Syringomyelia (cavity) is a complication of arachnoiditis, probably arising due to the pressure dissociation between the subarachnoid space and the central canal. It must be stressed that it does not occur in all cases of arachnoiditis.
A further, uncommon, complication is communicating hydrocephalus. This is thought to be due to alterations in the cerebrospinal fluid dynamics, due to the effects of the scarring in the subarachnoid space.
Arachnoiditis may, in a minority of cases, involve the brain as well as the spinal cord.
There are also subdivisions of the condition called rhinosinugenic arachnoiditis and optochiasmatic arachnoiditis, which are rare forms principally affecting the brain.
THE IATROGENIC ASPECT OF ADHESIVE ARACHNOIDITIS
PROGNOSIS
Arachnoiditis has been described as an insidious disease that is incurable. Guyer’s paper on the prognosis of arachnoiditis suggests that there tends to be a spectrum of the course of the disease, which varies from mild and nonprogressive, to a fulminating progression that may cause paralysis and even death. Wilkinson believes that progression after the first 24 months is unlikely to be due to the disease process alone. Most authors state that its onset may be years after the precipitating cause.
In general, arachnoiditis presents a highly variable clinical picture, with a fluctuating course. Some patients seem to reach a “plateau” and stabilise without further deterioration, whereas there is a group of patients who develop a relatively rapid progressive deterioration (within a matter of months) during which they tend to lose function in the affected limb(s).
THE SYNDROMIC NATURE OF SYMPTOMS IN ADHESIVE ARACHNOIDITIS
Adhesive arachnoiditis presents with diverse symptoms, which may relate to problems outside the CNS, and could therefore be described as a syndromic picture. However, bearing in mind that the treatments used for the neurological symptoms may cause a variety of side-effects, it is difficult to say exactly which symptoms can be directly and solely ascribed to arachnoiditis and which are more complex in origin.
The medical literature mostly describes symptoms in the lower back and or legs, with pain, weakness and sensory loss. Some authors also discuss bladder and sexual dysfunction. Jenik et al described the symptoms as “predominantly syringomyelic sensory deficits”.
A recent symptom survey amongst the support group COFWA (Circle of friends with Arachnoiditis) involving 66 members, has shown that there are a wide variety of symptoms.
This section of the article will attempt to clarify the range of symptoms that may be experienced in arachnoiditis. It must, however, be stressed that many people with arachnoiditis will not have some of these symptoms, especially the uncommon ones.
The predominant and most distressing symptom of arachnoiditis is chronic, persistent pain which is primarily neurogenic (nerve generated) and thus difficult to treat.
This pain is transmitted from the dorsal root ganglia (DRG) in the spinal cord. In contrast with normal DRG, inflamed DRGs produce sustained pain impulse from any mild stimulus such as body movements or even breathing.
Pain tends to increase with activity. There is may be a delay after onset of activity, with a slow summation, to a point where the pain suddenly becomes unbearable and then persists once the activity has ceased. This can make it difficult for patients and physicians or physiotherapists to assess what is the tolerable level of exercise.
Pain may be due to other factors besides nerve damage. These include musculoskeletal secondary to disuse, overuse or compensatory use of muscle groups, due to alteration of spine dynamics. There may also be muscle tension due to being in pain, or increased muscle tone (spasticity) caused by nerve damage. Joint pain may be due to similar factors, or may be part of the autoimmune picture.
Many patients suffer from burning feet, in particular. The majority of patients also have transient shooting pains that may vary in intensity from an insect bite to an electric shock.
Another problem may be an enhanced response to painful stimuli. This is called hyperpathia and may lead doctors to conclude that the patient has a low pain threshold. In fact, there is not a lowered threshold, rather a raised one, but once it is reached the response is magnified. This is called “delay with overshoot”. This is particularly noticeable in “visceral hyperpathia” in which normal bladder and bowel sensation is diminished, but once the signals of fullness are perceived, there is burning pain and urgency. This can lead to embarrassing accidents, especially if there is also nerve damage to bladder or bowel causing overactivity or sphincter dysfunction.
The areas commonly affected by pain are:
- In most cases: lumbar, buttocks, legs (often both), feet, perineum, hip, abdomen.
- In some cases: arms and hands, neck, head and face, chest.
Tingling and numbness are common features. Other sensory symptoms include loss of proprioception (sense of limb position up or down in relation to ground). This can result in tripping and falls. Temperature perception is sometimes diminished. There may also be bizarre sensations such as feeling as if you are walking on broken glass, water running down the legs, or insects crawling over the skin. These can be very distressing and many patients are reluctant to admit them to their doctor. A minority of patients may suffer from tinnitus and/or vertigo. Vertigo of cervical origin has been described in one paper, with features of ataxia (unsteady gait).
Motor nerve damage may cause loss of muscle strength, especially in the lower back and legs, in some patients. In most cases with weakness, it is mild, but it may progress sufficiently in some patients to necessitate use of walking aids or even a wheelchair.
Also, many patients report that they fatigue quickly. There may be compensatory overuse of some muscle groups to allow the patient to walk, but this leads to the muscle fatiguing more rapidly than normal. This is similar to the picture seen in PostPolio Syndrome (PPS).
Increase in muscle tone is quite a common feature and makes the legs stiff, which may have an effect on mobility.
Muscle spasms and cramps may be violent and painful. Muscle twitches (fasciculations) are usually painless and transient.
A number of patients complain of symptoms suggestive of Restless Legs Syndrome, with nocturnal unpleasant sensations in the legs, accompanied by motor restlessness.
Less commonly there may be trouble swallowing, sometimes due to oesophageal muscle spasms.
A common component of the arachnoiditis syndrome is the effect on the autonomic nervous system. (responsible for regulating involuntary processes such as blood pressure and temperature, bladder and bowel function etc.)
Disturbance of this system occurs because the nerves involved run along the spinal cord in the “sympathetic and parasympathetic chains”(thoracolumbar and craniosacral respectively).
Bowsher’s paper on central pain describes how most patients with central pain develop “autonomic instability”, referring to increase of pain by physical and emotional stress, with cutaneous blood flow and sweating also being affected.
Ziegler et al describe how systemic diseases such as diabetes can cause peripheral sympathetic neuropathy, giving rise to postural hypotension, heat intolerance etc. They
also maintain that patients with diseases of the sympathetic nervous system demonstrate marked abnormal stress responses to minor stresses such as change of posture or ambient temperature.
Principal symptoms of autonomic dysfunction include:
Bladder, bowel and sexual dysfunction. These are often very distressing to patients.
Neurogenic bladder dysfunction may cause difficulty initiating urination and emptying the bladder, or hyperactive detrusor with sphincter disturbance causing incontinence. If the bladder is incompletely emptied (leaving a residual volume) there is a risk of recurrent urine infection. Detrusor hyperactivity can give rise to high bladder pressures and possible reflux of urine to the kidneys, with a risk of hydronephrosis. Either problem may be exacerbated by decreased bladder sensation, which may lead to overflow incontinence, especially if there is an element of visceral hyperpathia. There may also be nocturia. Drugs such as antidepressants (e.g. amitriptyline) may worsen bladder dysfunction, causing difficulty in initiating micturition and emptying the bladder.
Bowel function may also be affected. Constipation due to drug treatment (especially opiates) and decreased mobility may complicate the picture.
Dyspepsia and intermittent vomiting are relatively uncommon problems. They may be due to gastroparesis (delayed gastric emptying) similar to that seen in diabetic autonomic neuropathy. Symptoms of gastroparesis include postprandial nausea, epigastric pain/burning, bloating, anorexia and vomiting. There may be vomiting of undigested food in the middle of the night or in the morning prior to eating breakfast.
Sexual dysfunction may affect potency and ejaculation in men, as well as causing problems with orgasm in both sexes.
Blood pressure disturbance (high, low or fluctuating); this may cause dizziness, syncope, or headaches. Orthostatic (postural) hypotension may occur. Mathias describes how in chronic autonomic dysfunction, pressor stimuli such as mental arithmetic, isometric exercise and cold, do not result in the normal increase in blood pressure. Also, stimuli such as food ingestion, which would normally activate the sympathetic system to maintain blood pressure, tend to actually cause marked hypotension.
Khurana discussed cases with chronic cervical myelopathy who responded to orthostatic challenge with hypotension, followed by hyperhidrosis (excess sweating), hypertension and chills.
Very rarely, there may be autonomic dysreflexia as seen in spinal cord injuries, with paroxysmal hypertension due to excess sympathetic activity reflexly activated by bladder or bowel distension, as described by various authors.
Other cardiovascular symptoms include palpitations.
Cold extremities (Raynaud’s type phenomenon) are a common vasomotor problem. (Note: Raynaud’s is also seen in autoimmune disorders such as lupus:)
Sudomotor effects of hyperhidrosis or anhydrosis (increased or absent sweating) may impact on temperature regulation, which is a common problem. Hyperhidrosis may be compensatory for loss of sweating in another area, or may be the initial phase before progression to anhydrosis.
An uncommon problem may be facial pain, loss of sweating on one side of the face and change in size of one pupil (Horner’s syndrome). There are also isolated reports of Adie’s tonic pupil.
The following group of symptoms is reflective of the inflammatory nature of the condition and may point to an autoimmune component:
Most arachnoiditis sufferers experience a fluctuating course of symptoms, with intermittent “flare-ups” and periods of relative remission.
Some sufferers have intermittent low-grade fevers, malaise and raised ESR (SED) and/or white cell count. These laboratory indices are both indicative of a nonspecific inflammatory process. Auld mentions fever and chills as part of the syndrome of chronic spinal arachnoiditis.
They may also have lymphadenopathy (enlarged lymph glands).
A common feature is skin rash, often unexplained. Often this is urticarial (hives) or there may be angio-oedema, both suggestive of an allergic-type reaction. A few patients develop photosensitivity, but this may be related to medication.
Joint pains are also common, not just in weight bearing joints, but also small joints. Rarely, there may be neurogenic arthropathy (Charcot joint), due to loss of sensation around the joint. (This is also seen in peripheral neuropathies such as diabetic neuropathy.)
A number of patients complain of dry eyes and mouth (as seen in Sjogren’s syndrome) but this is likely to be due to side effects of medication in most cases.
Other eye problems include iritis and uveitis, both inflammatory conditions seen also in association with autoimmune diseases.
It is likely that the features of myofascial pain and malaise are part of the arachnoiditis syndrome itself rather than a separate condition.
A minority of patients also has a diagnosis of an autoimmune disease in conjunction with their diagnosis of arachnoiditis. These include Systemic Lupus Erythematosus, Sjogren’s syndrome, Thyroiditis, Sweet’s syndrome, Rheumatoid Arthritis, Primary Biliary Cirrhosis and Crohn’s disease. This is an area for further investigation.
It is also apparent that a small number of sufferers develop multiple drug allergies, which is also seen in autoimmune conditions such as lupus.
Miscellaneous problems such as osteoporosis (c.f. in RSD, or due to decreased mobility) low potassium (possibly due to medication), chest pain mimicking angina, recurrent sinusitis, dyspnoea (shortness of breath) are seen in a few patients.
Eye problems (see autoimmune symptoms) seem to be quite common, with patients who have undergone myelography complaining of photoaversion (intolerance of bright light). Some patients describe stabbing pains or tingling and seeing “stars”. There is an increased incidence of migrainous type headaches, often with auras. It should be noted that there is an association between photoaversion and anticonvulsant treatment, particularly phenytoin and carbamazepine.
Recurrent dental problems are quite common. Many patients undergo repeated root canal procedures but continue to suffer from facial pain and odontalgia (tooth pain) without attributable dental pathology. A number of patients also suffer from bleeding gums (periodontal disease) and a few have “burning mouth syndrome”. It is possible that some of these problems are related to medications that cause dry mouth, the lack of saliva contributing to reduced protection against infection and caries. The burning mouth symptoms could have a neuropathic component.
Dysphagia (difficulty swallowing) may affect some patients, especially those who have cervical pathology. In particular, this may occur if there is arachnoiditis accompanied by degenerative changes such as anterior osteophytes (bony outgrowths). However, it may also be experienced by those with only lumbar pathology, though the reasons are unclear.
Pharyngeal symptoms may include feeling as if a lump is stuck in the throat, and this may be dismissed by some clinicians as “globus hystericus”, a psychosomatic complaint.
Fatigue is a very common complaint, and can be due to a variety of factors.
Weight gain is a common problem. This is largely to do with decreased mobility and possibly to fluid retention secondary to medication (from drugs such as: Amitriptyline, Gabapentin, Ibuprofen, Morphine and other opiates, prednisolone/methylprednisolone).
Alternatively, some patients may suffer weight loss, due to general debility and often, poor appetite.
The cognitive effects of arachnoiditis are anxiety and reduced ability to think clearly, with some short-term memory impairment. These are usually in direct proportion to the pain level being experienced.
Sleep disturbance is common, and usually directly related to pain. It may contribute to depression, which is an understandable reaction to intractable pain, loss of function, loss of role and job, financial and relationship problems as seen in other chronic, debilitating conditions. Fear for the future (prognosis cannot be predicted) and uncertainty about the diagnosis substantially increase this problem.
Many sufferers are reluctant to admit to depression, as they fear that their more unusual symptoms may be more readily dismissed by doctors as a product of their mental state.
DIFFERENTIAL DIAGNOSIS
Essentially, this involves excluding other causes of FBSS, such as recurrent disc herniation, disc fragments, stenosis, spondylosis or epidural fibrosis.
However, other causes of polyneuropathy should also be considered, especially those of an autoimmune origin.
It is interesting to note that a number of patients have a dual diagnosis of arachnoiditis and Multiple Sclerosis (MS). This is presumably due to some similarities between the two conditions.
Fibromyalgic symptoms are likely to be part of the arachnoiditis syndrome, as opposed to being due to a separate disease entity.
LOOKING TO THE FUTURE
Dr. Charles Burton has called arachnoiditis a “scientific orphan”. As yet, systematic, coordinated research is lacking.
Areas for future research include:
1.Autoimmune aspects
Aetiology (causes)
Pathology (disease process)
Possible treatments
2.Developments in treatment of neuropathic pain
Other projects include:
- Raising public and medical awareness of the syndromic nature of arachnoiditis and of the adverse effects of various types of invasive procedures.
- Working towards a collaborative approach amongst specialists such as neurologists, neurosurgeons, orthopaedic surgeons, immunologists, physiotherapists, and sufferers, to further understanding of this debilitating condition.
Dr. Sarah Smith MB BS, Patron of the Arachnoiditis Trust.
March 1999.
APPENDIX I: AUTOIMMUNE ASPECTS
MacDonald noted that 18% of the general population carry a factor in the blood (Histamine Release Factor HRF) which causes a dramatically potentiated, sustained autoimmune reaction to foreign substance in the people who carry this factor. As this factor may be implicated in autoimmune responses, this may be relevant in explaining why there is only a minority of patients with arachnoiditis who develop the condition to a clinically significant degree.
There seems, from anecdotal evidence, to be a significant proportion of arachnoiditis patients who have autoimmune problems.
Vasculitic neuropathies are seen in Rheumatoid Arthritis, Sjogren’s, Behcet’s syndrome and Systemic Lupus Erythomatosus. The commonest disorder that seems to be diagnosed concurrently with arachnoiditis is Sjogren’s syndrome. Various authors describe neurological aspects of this disorder, although there has been no direct reference to a link with arachnoiditis, however, there are similar clinical features between the two conditions. Kumazawa et al attribute the chronic sensory neuropathy occasionally seen in Sjogren’s to dorsal root ganglionitis with T-cell invasion. They also describe autonomic dysfunction in Sjogren’s syndrome.
Nitsche et al suggest that neurological features are seen frequently in overlap syndrome (a clinical picture of multiple coexistent autoimmune disorders, also known as Mixed Connective Tissue Disease MCTD), and that occasionally a demyelinating type
picture of central nervous system involvement may be seen. It is possible that arachnoiditis is part of the clinical spectrum of MCTD.
Tesavibul suggests that there are subsets of Multiple Autoimmune Syndrome (MAS) and of particular interest is his proposed Type 2, which includes Sjogren’s syndrome, Rheumatoid arthritis, Primary Biliary Cirrhosis, Scleroderma and Autoimmune thyroid disease. (There are isolated cases of each of these disorders seen in patients with arachnoiditis).
There is also a recognised, albeit rare, association between the chronic inflammatory condition, sarcoidosis, and arachnoiditis. Sarcoidosis is a multisystem, chronic granulomatous (a specific type of chronic inflammatory) disorder, which involves an abnormal immune response. The exact source of this reaction is as yet unknown. A study by Sharma showed 24% of neurosarcoidosis cases had meningeal involvement.
Marinac noted that there appears to be an association between the occurrence of hypersensitivity-type reactions in drug and chemical induced meningitis (an acute reaction) and underlying collagen vascular disease (known to be autoimmune).
It has been seen in conditions such as Rheumatoid Arthritis that there may be anti-plasminogen antibodies (plasminogen is part of the fibrinolytic pathway).
It may therefore be possible that arachnoiditis involves an autoimmune process that affects fibrinolysis.
A recent papers suggests that in arachnoiditis there is a similar process of inflammation to that seen in serous membranes such as the peritoneum, with “a negligible inflammatory cellular exudate and a prominent fibrinous exudate”. It is worth noting that the condition retroperitoneal fibrosis may be seen in association with rheumatoid arthritis.
APPENDIX II: SYRINGOMYELIA
The principle features are:
- Headache- worsens with cough, sneeze, and strain.
- Neckache
- Pain in upper limbs, often exacerbated by valsalva manoeuvres, exertion or coughing.
- Areas of dissociated sensory loss, which may be in a bizarre distribution over the trunk and upper limbs.
- Loss of temperature sensation in upper limbs may lead to painless burns.
- Loss of upper limb reflexes; positive Babinski reflex
- Atrophy (wasting) of small muscles in the hands
- Spastic paresis, gradually progressive, leading to difficulty in walking. (increased muscle tone and weakness)
- Uncoordinated movements
- Muscle spasms and fasciculations (twitches)
- Skin rashes
- Alteration in sweating
- Raynaud’s phenomenon (cold, painful hands due to poor circulation)
- Horner’s syndrome (see above), nystagmus.
- Dysphagia (difficulty swallowing)
- Dysphonia (abnormal voice)
- Abnormal salivation.
(These symptoms are sometimes seen in uncomplicated arachnoiditis. Jenik et al (xxv) stated that spinal cord syndromes due to non-traumatic adhesive arachnoiditis cause “predominantly syringomyelic sensory deficits.”)
Later stages may affect bladder, bowel and sexual function.
- Joint pains worse with straining.
- Charcot Joints (neurogenic arthropathy= joint damage due to lack of protective sensation)
- Symptoms may be unilateral or bilateral.
- An uncommon finding is onset of electric shock sensation running up and down the spine when the head is flexed or extended, occasionally followed by syncope (passing out). This is known as Lhermitte’s phenomenon.
- Some patients may show an increasing scoliosis (lateral curvature of the spine) which is thought to be due to unequal nerve supply to the paraspinal muscles.
Misdiagnoses have included:
- Carpal tunnel syndrome (neurological symptoms resulting from compression of the median nerve at the wrist)
- Ulnar nerve compression (ulnar nerve in the arm)
- Cervical spondylosis (degenerative disease of the cervical spine).
- Diagnosis is by MRI scan of the spine and EMG tests (electrical tests to detect muscle weakness)
ADDENDUM
It is no longer considered necessary to use a contrast agent in MRI scanning provided that the scan is T2 weighted, high resolution preferably with a stir cycle. Although this scan is considered the diagnostic test, it must however, be remembered that not all scans are sensitive enough to detect arachnoiditis, especially in the early stages. In any case, as regards MRI as a tool to assess the severity of the condition, it is comparable to using a chest X-ray to determine the heart rate and rhythm. Therefore, other tests such as Electromyograms (EMG) and nerve conduction studies (NCV) may be very useful in assessing the extent of nerve impairment.
Sarah Smith, MAY 2000.
Learning to Live Again with Arachnoiditis 