painmanagement - practical neurologyv2.practicalneurology.com/pdfs/pn0707 pain mngmnt.pdf ·...

Fibromyalgia: Should Neurologists Treat This Condition?

By Charles Argoff, MDPAINMANAGEMENT

It’s widespread, affecting three to six percent of the population. But is it within the purview of neurology? New drug approvals should help.

You’re asked to see a 45-year-oldfemale whose chief complaint isof chronic headache, chronicwidespread muscle and jointpain, difficulty with sleep and

chronic low back pain. She is referred toyou by her primary care physician who hascompleted detailed laboratory testing; allresults, including those for autoimmune/inflammatory disorders, all negative. Allradiographic testing is also negative. Thepatient is finding it difficult to workbecause of her pain and other relatedsymptoms. A formal neurological exami-nation reveals widespread tenderness butnot focal neurological signs/deficits.

You see another patient who is a 35-year-old male with chronic widespreadmusculoskeletal pain and complains ofuncertain etiology. He is no longer able towork as a carpenter, has no history ofdepression or anxiety, and is married. Hedenies substance abuse. His symptomsbegan shortly after injuries he sustainedfrom playing soccer in a local adult league.His entire work-up has been negative; afamily doctor, orthopedist, rheumatologistand now you have seen him.

Assume both carry the diagnosis offibromyalgia, arrived at via the AmericanCollege of Rheumatology (ACR) criteria.Should you as a neurologist treat thesepatients, or should they be referred back toa primary care physician, to a rheumatolo-gist, or perhaps to a pain specialist?

Pinpointing PainFibromyalgia is a chronic pain syndromecharacterized by diffuse muscle, joint orbone pain as well as a wide range of othersymptoms. Recent studies suggest that

people with fibromyalgia may be geneti-cally predisposed to develop this. It clearlyaffects more females than males, with aratio of 9:1 by the ACR criteria. Three tosix percent of the US population is esti-mated to have fibromyalgia, and it is mostcommonly diagnosed in individuals be-tween the ages of 20 and 50, though onsetcan occur in childhood. Although the dis-ease is not life-threatening, the degree ofsymptoms may vary greatly from day today with periods of flares or remission.

What are some of the symptoms/signsthat patients with fibromyalgia experi-ence? They often awaken feeling tired,despite having slept a sufficient number ofhours to provide an adequate amount ofsleep. Studies have shown that this is theresult of a sleep disorder in which deepsleep is frequently interrupted by bursts ofbrain activity similar to wakefulness.Fibromyalgia patients may consequentlyhave an insufficient deep restorative stageof sleep. Restless legs syndrome may alsobe associated with fibromyalgia. Con-stipation, diarrhea, abdominal pain andbloating may be seen in patients withfibromyalgia as well. Headache, facialpain, heightened sensitivity to odors andother sensory stimuli, depression, drymouth, dizziness, chest pain also havebeen reported in fibromyalgia patients.

The proposed pathophysiology focuseson the role central sensitization might playin this syndrome. Why this occurs isunclear, although abnormalities of variousneurotransmitters have been determinedand well-designed fMRI studies demon-strate sensory abnormalities in patientswith fibromyalgia. Risk factors forfibromyalgia include female gender, histo-

ry of rheumatologic diseases such as lupusor rheumatoid arthritis, and a family his-tory of the condition.

In my experience, fibromyalgia is bothover- and under-diagnosed. The first stepin making the diagnosis is to consider alldiagnoses that can explain the patient’ssymptoms and consider, at least for now,fibromyalgia as a diagnosis of exclusion. Inthis regard, neurologists play a pivotal role.

Guidelines for diagnosing fibromyalgiaas developed by the ACR include havingwidespread aching at a minimum of 11 ofthese 18 tender points. However, not allphysicians agree with these criteria.Although fibromyalgia itself is not per se aprogressive disorder, the persistence ofpain, sleep disturbances and other symp-toms can lead to progressive functionalimpairment and its obvious consequences.

Treatment OptionsSo, back to the patients mentioned above.You have completed your evaluation andhave dictated your note—why wouldn’tyou offer treatment to these patients?Although fibromyalgia has no knowncause and its pathophysiology is uncertain,there is now at least one FDA approvedtreatment for fibromyalgia, and additionalagents may be approved in the future.

Pregabalin (Lyrica) was approved forthe treatment of fibromyalgia just lastmonth. Studies that led to the FDAapproval as well as data recently presentedat the 2007 AAN Annual Scientific meet-ing in Boston have demonstrated that pre-gabalin may reduce pain and improvefunction in people with fibromyalgia.Pregabalin is also FDA approved for thetreatment of neuropathic pain associated

20 Practical Neurology July 2007

• History of widespread pain has been present for at least three months. Painis considered widespread when it occurs in both sides of the body and aboveand below the waist. In addition, axial skeletal pain (cervical spine, anteriorchest, thoracic spine or low back pain) must be present. Low back pain isconsidered lower segment pain.

• Pain in 11 of 18 tender point sites on digital palpation performedwith an approximate force of 4kg. A tender point has to be painful atpalpation, not just “tender.” See diagram to the right.1&2: Occiput at the suboccipital muscle insertions. 3&4: Low cervical at the anterior aspects of the intertransverse spacesat C5-C7. 5&6: Trapezius at the midpoint of the upper border. 7&8: Supraspinatus, at origins, above the scapula spine near themedial border. 9&10: Second rib at the second costochondral junction, lateral to the junctionson the upper surfaces.11&12: Lateral epicondyle 2cm distal to the epicondyles. 13&14: Gluteal in upper outer quadrants of buttocks in anterior fold of muscle. 15&16: Greater trochanter posterior to the trochanteric prominence. 17&18: Knee at the medial fat pad proximal to the joint line.

Source: American College of Rheumatology, 1990

July 2007 Practical Neurology 21

with diabetic polyneuropathy, post-her-petic neuralgia as well as an anticonvulsantfor the treatment of seizures. Studies haveshown that pregabalin reduced signs andsymptoms of fibromyalgia in some, butnot all, patients. Approximately half of theparticipants in one study who were takingthe highest allowed doses of the drugreported at least a 30 percent improve-ment. Side effects of pregabalin includedizziness, sleepiness, difficulty concentrat-ing, blurred vision, weight gain, drymouth and peripheral edema.

Duloxetine (Cymbalta)—an SSRI-typeantidepressant that’s FDA approved forthe treatment of diabetic peripheral neuro-pathic pain, major depressive disorder andgeneralized anxiety disorder—is activelybeing developed as a treatment offibromyalgia. Multiple published studiessupport the use of duloxetine for the effec-tive treatment of fibromyalgia; however, itis not yet FDA approved for this indica-tion as of this writing.

Minalcipran is also a selective norepi-

nephrine serotonin reuptake inhibitingtype of antidepressant that is being devel-oped for fibromyalgia treatment. How-ever, it is not currently FDA approved forany condition and therefore is not com-mercially available in the US.

Traditionally, simple analgesics such asacetaminophen and nonsteroidal anti-inflammatory agents have been used tohelp control the pain associated withfibromyalgia, as have various other antide-pressants, muscle relaxants, sleep aids andopioids. Nonmedical treatments have alsobeen prescribed including cognitivebehavioral approaches, acupuncture, chi-ropractic care, hypnosis and numerousherbal remedies.

A word of caution regarding the use ofopioid analgesics in this setting. Althoughstill not completely understood with manydetails to be worked out, the use of opioidshas been reported (especially in animals)to be associated with the risk of the devel-opment of opioid-induced hyperalgesia.Many fibromyalgia experts therefore

strongly urge restraint in prescribing theseagents with careful monitoring of patientsin this setting. In addition, while effectivesleep is important, one wants to avoid cre-ating a situation where the patient be-comes dependent on such agents.

Clearly, this is only the beginning;however, the recognition of fibromyalgiaas a condition for which specific treat-ments can be developed and which theFDA recognizes has occurred. Neuro-logists are familiar with the only currentlyapproved drug for this condition and arealso familiar with a treatment in develop-ment. Neurologists should strongly con-sider not only playing a pivotal role in thediagnosis of fibromyalgia but also beingdirectly involved in the ongoing treatmentof patients with this condition. PN

ACR Criteria for Fibromyalgia Diagnosis

Charles Argoff, MD is AssistantProfessor of Neurology at New YorkUniversity and a frequent lecturer onpain medicine.

3

9 10

4

1211

17 18

1 2

15 16

13 14

5 6

7 8