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10 Articles in Volume 12, Issue #6
Carpal Tunnel Syndrome
Case Studies in New Daily Persistent Headache
Hormone Testing and Replacement in Pain Patients Made Simple
Management of Prenatal Low Back Pain
Managing the Diabetic Patient with Dementia
Myofascial Pain Syndrome: Uncovering the Root Causes
New Tools for Improving Patient-to-Physician Communication in Clinical Practice
Suicide and Suffering In the Elderly: We Must Do Better
Three Cases Highlight the Challenges Of Treating Rheumatoid Arthritis
Understanding the Sources of Morphine

Case Studies in New Daily Persistent Headache

New daily persistent headache often is difficult to treat, with identifiable triggers ranging from head trauma to surgery to infection.

Both cases in this Case Challenge are summarized below, followed by a discussion of treatment options.

Case 1 : Adult
Jack is a 42-year-old male with no prior history of headaches or migraines and is in good overall health. Two years ago, he awoke with a mild headache, which became severe as the day progressed. He had been experiencing cold-type symptoms for about a week, had been under severe stress, and was not sleeping well. Jack now suffers from a moderate daily headache that is continuous 24/7.

A workup by his general practitioner was completely normal. He visited a succession of doctors—his chiropractor, acupuncturist, physical therapist, dentist, and psychotherapist—all to no avail. He was prescribed various analgesics and headache preventives over the next two years, but found nothing that helped. After two years, a neurologist diagnosed Jack with new daily persistent headache (NDPH). Jack has lost his job due to the head pain, and his marriage is suffering.

Case 2: Adolescent
Rose is a 17-year-old female with no history of headaches. She presented with a severe headache that began suddenly during final exams of her junior year. A perfectionist, Rose is a straight-A student who puts enormous pressure on herself. Rose has moderate anxiety, but no depression. She has a history of irritable bowel syndrome (IBS), which worsens under stress. Prior to visiting a headache specialist, she had not had a recent work-up, nor had she seen an ophthalmologist. Her continuous headaches have interfered with school, and she is now home schooled.

Her work-up—consisting of laboratory testings, magnetic resonance imaging (MRI), and an ophthalmological exam—was normal. The anticonvulsant topiramate (Topamax), which is FDA-approved as a preventive medication for migraines, was titrated to 150 mg, but it did not help and produced intolerable side effects. The tricyclic antidepressant amitriptyline did help, but Rose gained weight and was very tired. Various abortive agents (triptans, non-steroidal anti-inflammatory drugs, etc) were used, but none were particularly helpful. A psychologist trained Rose in biofeedback, which was somewhat helpful for her head pain and IBS.

New daily persistent headache (NDPH) is one type of chronic daily headache, along with chronic migraine, chronic tension headache, and hemicrania continua. NDPH is being increasingly recognized as an important type of headache, both because of the frequency and also the refractory nature of the head pain.

NDPH develops quickly, usually within hours or one day—but within three days the headache must be constant.1 Many patients remember exactly what they were doing when the headaches began. The pain is usually bilateral, with aching pressure and/or throbbing. The intensity may vary from mild to severe, but tends to be mild to moderate. The headache is usually constant. At least half of patients describe migraine-associated features, such as nausea, phonophobia, lightheadedness, photophobia, etc. Allodynia, often seen in chronic migraine, is present in approximately a quarter of patients.2 Autonomic symptoms (nasal stuffiness, conjunctival injection [swollen, red eyes], etc) may occur.

NDPH is somewhat a diagnosis of exclusion. Infection (including meningitis and sinusitis), mass lesions, subdural hematomas, cerebral venous thrombosis, low or high cerebrospinal fluid (CSF) pressure headaches, arteritis, arterial dissection, post-traumatic headaches, etc, all need to be excluded.3 Usually the history, along with an MRI/magnetic resonance angiogram, will exclude these entities. There are several newer proposed diagnostic classifications; generally, diagnosis includes:

  • At least three months of sudden-onset headache
  • No significant remission
  • Exclusion of other disorders4

NDPH is unilateral in a small number of patients, and if this occurs with autonomic symptoms, it may represent a variant of hemicrania continua.

While we do not know the pathophysiology of NDPH, central nervous system (CNS) inflammation is one possibility. Tumor necrosis factor α (TNF α) has been implicated in neuroinflammation. TNF α is a cytokine that enhances inflammation. In one study, CSF evaluations of NDPH patients resulted in almost all samples showing an increase in CSF TNF.5

Glial cell disruption may play a role; glial cells manufacture CNS cytokines. Glial cells are very sensitive to viral infection and stress; surgery may impact glials as well.6 Cervical joint hypermobility, along with hypermobility of other joints, may play a role.7 Patients with NDPH often are tall and thin, with long necks.

Chronic daily headache (CDH) occurs in approximately 3.5% of the population, but the prevalence of NDPH is not known. One study from a headache center concluded that 10.8% of 638 CDH patients had NDPH.8 A similar study in the pediatric population revealed that, among those with CDH, 13% had NDPH.9 The prevalence of NDPH may well be greater among adolescents than in adults. Females outnumber males with NDPH by approximately 2.5 to 1.3 Most patients do not have a previous history of headache. A prior history of anxiety or depression is seen in about half of the NDPH patients.3 After the onset of NDPH, many patients experience depression.

Triggering Events
Approximately 50% of patients have an identifiable trigger. Stress may be a trigger in some patients. Infection, particularly viral, also is often cited as a trigger.1 In one study, the Epstein-Barr virus was implicated as an initiating culprit.10 Exposure to certain toxins may also precede the onset of NDPH. Surgical procedures have occasionally triggered the onset of NDPH. Head injury, even when mild, may be an initial event. Cervical trauma or other pathology, particularly in those who have thin necks with cervical hypermobility, may initiate the onset of NDPH.

NDPH is more resistant to treatment than is chronic migraine, which is usually transformed migraine (slow onset over years). The usual daily preventive migraine medications are given, as they may be helpful for some NDPH patients. These include tricyclic antidepressants (amitriptyline [Elavil], protriptyline [Vivactil], others), anticonvulsants (valproic acid [Depakote], topiramate [Topamax], others), antihypertensives (β blockers, calcium channel blockers, others), Petadolex (natural butterbur), selective serotonin reuptake inhibitors (fluoxetine, sertraline, others), serotonin-norepinephrine reuptake inhibitors (duloxetine [Cymbalta], venlafaxine, others), and muscle relaxants (tizanidine [Zanaflex], others).11

Botulinum toxin A may be helpful as well; however, there are no published controlled trials of treatment. Benzodiazepines, particularly clonazepam, have had some limited success. Intravenous dihydroergotamine is more likely to be of help with chronic migraine. A course of high-dose IV corticosteroids, followed by oral steroids, has shown some promise, but the high doses can predispose to serious side effects.12 Intravenous magnesium may provide short-term relief. Doxycycline, given over several months, may help some patients with NDPH. Greater occipital nerve blocks sometimes are useful, particularly with unilateral headaches.

Outside of medication, psychotherapy is worthwhile for those with anxiety or depression. Biofeedback is helpful for some headache patients. Exercise is always encouraged, as is yoga and Pilates. Acupuncture, physical therapy, or chiropractic therapy may help for some patients.

While the results of treatment may be discouraging, it is crucial to stick with the patient, continue to try different medications or modalities, and not give up on the NDPH sufferer.

Long-term Prognosis
Several studies have evaluated long-term outcomes. One study revealed that, after two years with NDPH, about 25% of the patients were free of headache, and 66% had at least a 50% reduction in headaches over time.13 Another study reported that 76% of patients continued to have headaches over time, while 15% remitted; median time to remission was 21 months. Among study participants, 8% had a cyclic form, with a relapsing-remitting pattern. A small study of children and adolescents discovered that eight out of 28 patients were free of headache within one to two years, while most (20) continued to suffer long term from head pain.14

NDPH is an important category of headache, as it is often difficult to treat, and results in considerable disability. It is unique in that more than 50% of patients have an identifiable trigger, although these range from infection to surgery to head trauma. We are just beginning to identify the pathophysiology that leads to NDPH. Treatment of NDPH is scattershot and varied at present; further studies will undoubtedly lead to more effective therapies.

Last updated on: August 2, 2012
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