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Neurologists Weigh In On Why Treatment Often Fails

Many physicians and neurologists fail to rule out all potential causes of persistent headaches or explore available treatment options, even when patients exhibit comorbid symptoms that should raise red flags, according to a group of leading headache experts.


Dr. Richard B. Lipton

In a paper published in April, neurologists at several major hospital headache centers examined why treatment so often fails, and presented a systematic approach to accurate diagnosis and treatment (Neurology 2003; 60:1064–1070). The authors found that many patients with daily or near-daily headaches are not receiving adequate examinations or treatment.

“This is an attempt by a group of leading headache neurologists to summarize what we have encountered in our specialty practices,” said lead author Richard B. Lipton, MD, Professor of Neurology at Albert Einstein College of Medicine of Yeshiva University, in New York City.

“We believe that the vast majority of patients with refractory headaches have a biologically determined problem that has either been misdiagnosed, is mistreated, or is simply very difficult to treat,” he said. “The most common reason is that an important headache trigger has been missed.”


Dr. Lipton pointed out that the Neurology article was not a research paper. “It is a partial checklist that we use in our practices,” he said. “Many patients are referred from primary care physicians who just don't have the experience and knowledge of headaches and their treatment that we can offer. If a patient is not doing well with whatever treatment they have received, we are offering a list of things that should be checked.” (See sidebar on page 9 for list.)

In a study published last year (Neurology 2002;58(8):446–450), Dr. Lipton and his colleagues reported that, although 28 million people suffer migraine headaches, less than half seek medical treatment or receive the latest medications that might relieve attacks.

The new report identifies and discusses five of the most common reasons why headaches are misdiagnosed, together with typical and unusual symptom profiles and treatment strategies. Co-authors include neurologists at the New England Center for Headache in Stamford, CT; the Michigan Head Pain and Neurological Institute in Ann Arbor; London's National Hospital for Neurology and Neurosurgery; and the Jefferson Headache Center at Thomas Jefferson University Hospital in Philadelphia, PA.

Persistence is the key to accurate diagnosis and treatment, said Dr. Lipton, who noted that the team approach used by many US subspecialty centers can help reduce the burden of caring for difficult cases. These teams typically include nurses, fellows, physician's assistants, and psychologists who can provide diagnostic support and educate patients. Inpatient programs are recommended for carefully selected patients for whom outpatient treatment is unsuccessful.


“Doctors need to revisit their initial diagnosis, recheck possible triggers, and make sure the drug regimen they are using is adequate and being followed,” Dr. Lipton said. “In the primary care setting, I think most misdiagnosis and treatment shortcomings are due to a lack of knowledge. Part of the trap is that once a patient is diagnosed at an initial visit, many doctors don't go back to square one and look at other possible headache factors. I've made that mistake myself.”

The rebound effect from medication overuse is the most common remedial problem associated with intractable headaches, he said, although there are many other possible causes that must be investigated. A critical profile of the headache should include the circumstances of its onset, as well as the character, speed of onset, and the patient's age.


The typical unresponsive headache patient usually will have had a number of neuroimaging procedures, but diagnostic testing should also reconsider conditions sometimes missed by CT or MRI scans. For example, imaging of the sphenoid sinus is often overlooked but recommended if sphenoid sinusitis is suspected. Physical exams should always include the eyes, ears, throat, and neck, and radiologists should be instructed to target other suspected sites of neuropathology such as the occipito-cervical junction, as well as the sella turcica and nasopharyngeal regions.

Misdiagnosis of primary headache is another common reason for intractability. Primary headache disorders that are often misdiagnosed include hemicrania continua in patients with chronic unilateral headache; paroxysmal hemicrania mistaken for cluster headaches, especially in female patients; and hypnic or “alarm clock” headaches in elderly patients.

The hypnic headaches are characterized by short-lived nocturnal attacks of head pain that awaken patients typically at the same time each night, sometimes while they are dreaming. The authors say these headaches are now more common than previously thought, and they often respond to a 300-mg dose of lithium carbonate at bedtime, slow-release lithium or melatonin, caffeine, or 120 mg of verapamil before sleep.

For patients who continually fail to respond to different treatments, the authors advise a lumbar puncture to identify possible infectious or inflammatory responses that can result in aseptic or chronic meningitis. Neuroimaging does not obviate the need for lumbar puncture testing in such cases, they note.


Exacerbating factors are frequently not mentioned or are overlooked by headache patients and their physicians, says Dr. Lipton. Physicians must accurately assess each patient's use and overuse of over-the-counter (OTC) and prescription drugs; caffeine and alcohol; other lifestyle, hormonal, and dietary triggers; as well as psychosocial factors.

Many patients do not view OTC products as real drugs and will not report use or abuse unless specifically asked, while others fear reporting misuse to their examining doctor, said Dr. Lipton. It is therefore important that questions and physician attitudes be non-judgmental. Likewise, it is important to consider any occupational or environmental factors associated with intractable chronic headaches.


Dr. Lipton said perceived intractability is often the result of incorrect dosing strategies. “It is best to start preventive agents at a low dose and then gradually increase the dose until therapeutic effects, treatment-limiting side effects, or the ceiling dose is reached. At least several weeks are required to evaluate the success or failure of a treatment and further increases past the ceiling dose may be necessary if there is a partial response without side effects but the headaches remain disabling.”

The report also offers recommendations for treating patients with comorbid medical or neurological illness, both of which tend to occur more frequently in migraine sufferers. Major depression, anxiety, affective disorders, stroke, or epilepsy all affect headache treatment and impose therapeutic challenges for neurologists and generalists and limit treatment options.

Because the review is based primarily on anecdotal observations and reports, the authors stress the need for prospective, observational, and selective studies to further validate their understanding of treatment failure.


Responding to the report from the primary care perspective, Frederick G. Freitag, DO, Associate Director of the Diamond Headache Clinic in Chicago, IL, said in an interview that the Neurology article provided good discussion on the misdiagnosis of the primary disorders as well as the exacerbating factors that lead to medication treatment failures. But he felt the report overlooked some of the more common factors that lead to misdiagnosis – such as “plain old sinusitis” – and that it could have offered more help in determining which neuroimaging tests to use.

He also felt that the report “missed the mark” on non-pharmacologic therapies such as herbal therapies and the effect they may have on treatment.


Seymour Diamond, MD, founder and Executive Chairman of the Diamond Headache Clinic, had a more favorable view of the report and the checklist, however – both of which, he said, should prove valuable for physicians.

“There is a lot of headache advertising in this country, but not a lot of education about what causes headaches,” Dr. Diamond said. “Most doctors are trying to treat symptoms, not investigating possible causes. We need a disease-centered approach rather than one that is product-oriented, and we need to explain the disease much better.”


Dr. Diamond, who is a neurologist, said that patients with recurring headaches should not necessarily be referred to neurologists exclusively. “Migraines are not a one-time consultation,” he said. “They and other headaches require continuity of care. There are a lot of prophylactic drugs, but also a lot of issues that may be missed if doctors are relying exclusively on headache drugs – psychological aspects and other triggers – these, of course, take more than one visit.”

Dr. Diamond said that whoever sees the patient most regularly should take charge of headache treatment, whether it is an internist or general practitioner or even a woman's gynecologist.

“Most schools don't spend much time on the issue; usually just a short course or one-hour presentation. There are some diagnostic guides, but they are not very prevalent. We need more of an educational emphasis on headaches.”


The diagnosis is incomplete or incorrect

  • A secondary headache disorder goes undiagnosed
  • A primary headache disorder present is misdiagnosed
  • The number of headache disorders is not clear

Important exacerbating factors have been missed

  • Acute headache medication or caffeine overuse
  • Hormonal triggers
  • Dietary or lifestyle triggers
  • Psychosocial factors
  • Other medications

Pharmacotherapy has been inadequate

  • Ineffective drug
  • Excessive initial doses
  • Inadequate final doses
  • Inadequate duration of treatment
  • Combination therapy required
  • Poor absorption
  • Noncompliance

Nonpharmacologic treatment has been inadequate

  • Physical medicine
  • Cognitive behavior therapy

Other factors

  • Unrealistic expectations
  • Comorbid and concomitant conditions
  • Inpatient treatment required

Source: Neurology 2003;60:1069.