eMedicine from WebMD
 

eMedicine Specialties > Neurology > Headache and Pain

Chronic Paroxysmal Hemicrania

Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Jashvant Patel, MD, Medical Director, Department of Pain Medicine and Comprehensive Rehabilitation, Medical College of Pennsylvania Hahnemann University

Updated: Sep 3, 2009

Introduction

Background

Chronic paroxysmal hemicrania (CPH) is also known as Sjaastad syndrome. It was first described in 1974 by Sjaastad and Dale.1 In 1976, the term CPH was proposed by Sjaastad on the basis of the first 2 patients, who had daily (ie, chronic), solitary, limited attacks (ie, paroxysmal) of unilateral headache that did not shift sides (ie, hemicrania).2 CPH, which has been included in the International Headache Society (IHS) classification system since 1988, is much less common than cluster headache (CH).

The short-lasting primary headache syndromes may be divided into (1) headaches with autonomic activation and (2) headaches without autonomic activation. Headaches with autonomic activation include chronic and episodic paroxysmal hemicrania, CH, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome).

Pathophysiology

The mechanisms responsible for the pain in CPH remain unknown. Discussion of important features, such as unilateral intense headache, autonomic abnormalities, and effectiveness of indomethacin, may help in understanding the pathogenesis.3

The release of both trigeminal and parasympathetic neuropeptides during headache has been described.4 Activation of the ipsilateral trigeminovascular system may explain sudden unilateral headache and may lead to miosis, increased intraocular pressure (IOP), and other autonomic abnormalities.

Increased sweating and decreased salivation during attacks and inhibition of increased IOP by an alpha-blocking agent or stellate ganglion blockade suggest sympathetic involvement.

Increased tearing, nasal secretion, and miosis may be due to parasympathetic stimulation. Trigeminoparasympathetic activation during CPH attack has been suggested; increases in vasoactive intestinal peptide (ie, parasympathetic peptide) level have been reported. Levels of calcitonin gene-related peptide also are reported to be high during CPH attacks.

Pain and pressure threshold, nociceptive flexion reflex, and blink and corneal reflexes have been studied in patients with CPH. The corneal reflex thresholds have been found to be decreased bilaterally during CPH attacks. Increases in corneal temperature on the symptomatic side also have been reported; this finding may be due to increased ocular blood flow.

The effectiveness of indomethacin in CPH may be due partly to reduction of intracranial blood flow (via a nonprostaglandin mechanism) and partly to its anti-inflammatory effects.

These findings may indicate a primary central mechanism and a secondary involvement of peripheral factors, affecting both the sympathetic and parasympathetic systems.

Recent studies suggest crucial role of hypothalamus. Functional neuroimaging studies have demonstrated activation of hypothalamus in cases of trigeminal autonomic cephalgias.5,6

Frequency

United States

CPH is a rare syndrome, but the number of diagnosed cases is increasing. The prevalence of CPH is not known, but the relative frequency compared with CH is reported to be approximately 1-3%.

International

Many cases of CPH have been described throughout the world, in different races and different countries, including Australia, Czech Republic, Slovakia, Denmark, Italy, France, Mexico, Canada, Sweden, Germany, Poland, India, Spain, Brazil, South Africa, Norway, New Zealand, the United Kingdom, and the United States.

Mortality/Morbidity

Mortality rate and morbidity of CPH have not been reported, although the therapy of choice, indomethacin, is known to be associated with the risk of bleeding.

Race

CPH is not known to occur preferentially in any race. CPH has been described in Caucasians and black South Africans.

Sex

In the past, because of female preponderance, CPH was considered a disease of women. However, CPH has been reported in increasing numbers of men. A study conducted in 1979 reported a female-to-male ratio of 7:1, but a review of 84 patients in 1989 reported a female-to-male ratio of 2.3:1.

Age

CPH can occur at any age; mean age of onset is 34 years.7 The youngest patient described in the literature was aged 6 years and the oldest was aged 81 years.8,9 In one report, CPH beginning at age 3 years was described; however, it may have been related to ipsilateral occipital hemorrhagic infarction.10

Clinical

History

The pain is unilateral, always affects the same side, and is generally oculofrontotemporal in location. The literature does contain reports of a few unusual cases, for example, patients with bilateral symptoms and possible shift in the side of the headache when the CPH progresses from the nonchronic to the chronic stage.

  • The pain is usually most severe in the oculotemporal area, the forehead, and above or behind the ear. Occasionally, pain can radiate and involve the ipsilateral shoulder, arm, and neck.
  • Headache can appear at any time in patients with CPH, in contrast to CH in which the headache usually occurs at night.
  • During severe attacks, excruciating pain with throbbing, boring, pulsating, or clawlike character has been described. In contrast to patients with CH, patients with CPH usually sit quietly or may curl up in bed between attacks.
  • The attack frequency usually is 10-20 attacks per day and may range from 2-40 attacks per day. Attacks usually last 2-25 minutes, but they may last as long as 60 minutes. In one prospective study, mean attack duration was 13 minutes (range 3-46 min). In a retrospective study, the mean duration of attacks was 21 minutes (range 2-120 min).
  • CPH can be triggered by various stimuli, including neck movement, external pressure to neck, or other factors.
  • CPH attacks are accompanied by autonomic symptoms, mostly on the same side as the pain, such as red eyes, tearing, nasal congestion, and sometimes rhinorrhea. Occasionally, photophobia may be present, but gastrointestinal symptoms are very rare.
  • Recognizing the various stages and different patterns of CPH is important. For example, during severe frequent attacks, patients may describe a constant headache or persisting tenderness on the symptomatic side.
  • IHS diagnostic criteria for CPH include the following (slightly modified from the Headache Classification Committee, 198811 ):
    1. At least 50 attacks fulfilling the criteria mentioned below in 2-5.
    2. Attacks of severe unilateral orbital, supraorbital, and/or temporal pain always on the same side lasting 2-45 minutes
    3. Attack frequency more than 5 per day for more than half of the time (periods with lower frequency may occur)
    4. Pain associated with at least one of the following signs/symptoms on the symptomatic side:
      • Conjunctival injection
      • Lacrimation
      • Nasal congestion
      • Rhinorrhea
      • Ptosis
      • Eyelid edema
    5. Absolute effectiveness of indomethacin (150 mg/d or less)
    6. At least one of the following:
      • History, physical, and neurologic examination findings do not suggest any of several disorders that include organic headaches, headaches associated with drug withdrawal, metabolic disorders, and other conditions.
      • History and/or physical and/or neurologic examination findings do suggest such a disorder, but it is ruled out by appropriate investigations.
      • Such a disorder is present, but CPH does not occur for the first time in close relation to the disorder.
  • CPH may be present in nonchronic or chronic form, which is 4 times more common.
    • Nonchronic attacks are similar to chronic attacks but may be less severe and less frequent.
    • The term pre-CPH stage or prechronic was preferred initially on the basis of the assumption that all patients would develop chronic symptoms. However, approximately 20% of patients appear to remain in the nonchronic stage for long periods.
    • Before development of chronic symptoms, many patients (42%) pass through a nonchronic stage with attacks separated by intervals of complete remission.
    • Dividing CPH into unremitting and remitting forms may be appropriate. The unremitting form is the chronic form, which either is unremitting from the onset or evolved from the remitting form.

Physical

  • The pain is severe, and attacks are associated with autonomic features, such as lacrimation (62%), conjunctival injection (36%), ipsilateral nasal congestion (42%), rhinorrhea (36%), and eyelid edema (33%).
    • Lacrimation may occur bilaterally but is always more marked on the symptomatic side.
    • Occasionally, mild ipsilateral miosis may be observed during attacks.
  • Patients with CPH who had dissociation in pain and autonomic features also have been described.
  • No definite evidence points to a Hornerlike syndrome, such as that described in CH, but mild miosis and eyelid edema that may mimic ptosis may be observed.
  • Forehead sweating may increase on the ipsilateral side, and patients with generalized sweating have been reported.
  • The coexistence of CPH and trigeminal neuralgia is called CPH-tic syndrome; many cases of this syndrome have been reported.
  • Simultaneous occurrence of ipsilateral CH and migraine headache in patients with CPH also has been reported.
  • Perform a careful physical examination to evaluate pathological secondary headache.

Causes

No definite cause is known.

  • The past medical history in patients with CPH is usually unremarkable. History of head or neck trauma is reported in about 20% of cases, but these findings are similar to CH or migraine.
  • Occasionally, attacks may be provoked mechanically by bending or rotating the head and by applying external pressure against the transverse processes of C4-C5, C2 root, or the greater occipital nerve.
  • No familial disposition is known for CPH; families of affected individuals do not have higher incidences of CH or migraine than the general population.

Differential Diagnoses

Cluster Headache
Migraine Headache
Migraine Variants
Trigeminal Neuralgia

Other Problems to Be Considered

Differential diagnosis should include other headaches with major autonomic features (eg, SUNCT syndrome) and persistent headaches with milder autonomic features (eg, hemicrania continua [HC]).

Several paroxysmal indomethacin-responsive headache syndromes have been described, including HC, jabs-and-jolts syndrome, icepick headache, hypnic headache syndrome, benign cough headache syndrome, benign exertional headache, coital headache, and thunderclap headache.

Cervicogenic headache, facial neuralgia, and other rare disorders, such as the red ear syndrome, also are considered in the differential diagnosis.

Simultaneous occurrences of CPH and other disorders, including CH, trigeminal neuralgia (CPH-tic syndrome), and migraine, also have been reported. The crucial factor in the differential diagnosis is the absolute response to indomethacin.

The trigeminal-autonomic cephalgias include CH and paroxysmal hemicranias in which head pain and cranial autonomic symptoms are prominent. CH is the most important differential diagnosis.

CH has male preponderance, unlike CPH, which is more common in females. In CPH, frequency of attacks is higher, usually more than 15 in 24 hours, whereas CH has an attack frequency of 1-4 (maximum 8) in 24 hours. The duration of headaches is shorter in CPH (2-25 min) than in CH (15-60 min).
Finally, CPH can be distinguished by its response to indomethacin therapy, which is not seen in CH.

HC is a rare disorder characterized by continuous, unilateral, indomethacin-responsive hemicrania of moderate severity. These headaches last from minutes to several days and sometimes are associated with autonomic features. A noncontinuous form also has been described.

The SUNCT syndrome is a distinctive rare condition with male preponderance characterized by less severe pain but marked autonomic activation during attacks. The pain, usually in the frontal and periocular area, is intractable to medications, including indomethacin.

Recently, a unique, stereotypical, episodic headache disorder marked by long-lasting autonomic symptoms with associated hemicrania (LASH) has been reported. The autonomic symptoms clearly overshadowed the headache as the major component of the syndrome. Both types of symptoms responded to indomethacin.

Other disorders that may mimic CPH include infarcts, arteriovenous malformation, brain tumor (eg, frontal lobe tumor, meningioma of the roof of the cavernous sinus, pathological process in the region of the cavernous sinus, gangliocytoma near sella turcica, parasellar pituitary microadenoma), maxillary cyst, collagen vascular disorders, cervical radiculopathy, disk herniation, and carotidynia.

Workup

Laboratory Studies

  • Perform lab studies to evaluate structural, metabolic, and other secondary causes of headache and facial pain.
  • Baseline routine blood tests may be needed to exclude contraindications to certain drugs and to avoid complications from long-term use of various medications.

Imaging Studies

  • CT scan, or preferably MRI, of the brain may be needed to rule out structural pathology.
  • Findings of neuroimaging studies, including MRI, are usually normal in patients with CPH.
  • Consider MR angiogram or arteriogram, if necessary, for atypical presentations.
  • Electroencephalography, brain mapping, and other radiologic studies are not required for patients with typical presentations.

Other Tests

  • Indotest (indomethacin 50 mg IM test dose) may be a useful tool in assessment of unilateral headache. The diagnosis of CPH is extremely important because it may imply lifelong treatment with a potentially noxious drug. Perform indotest in a standardized manner.
  • No characteristic electrocardiographic patterns were found during attacks, but marked variations in heart rate and rhythm abnormalities, including bradycardia, sinoatrial block, bundle branch block with episodes of atrial fibrillation, and multiple extrasystoles, have been observed.
  • Orbital phlebography may be abnormal in some patients, but the significance of this finding has not been established.
  • In one study of 3 patients with CPH, a slightly lower cerebral vasomotor reactivity was observed in the medial and posterior cerebral arteries on both sides and in the anterior cerebral artery on the symptomatic side than in healthy subjects. These observations may imply an abnormal vascular reactivity in CPH.
  • As compared to CH, CPH attacks did not demonstrate any changes in visually evoked event-related potentials (ERPs), latencies, and amplitudes.12
  • Perform ophthalmic evaluation, if needed, to assess ocular pathology such as glaucoma or orbital pseudotumor.

Procedures

  • Consider lumbar puncture, if necessary, for atypical presentations.

Treatment

Medical Care

  • The treatment of choice for CPH is indomethacin, which has an absolute effect on the symptoms. Both episodic CH and CPH respond well to indomethacin.
  • Other medications that may provide relief include salicylates (aspirin), naproxen, prednisone, celecoxib, piroxicam, acetazolamide, and ergotamine. One prospective open trial conducted with 10 patients experiencing CPH suggests that acetylsalicylic acid (and probably naproxen and diclofenac) and verapamil (for prophylaxis) are the most effective second-line drugs. In another report, two teenaged girls who demonstrated dramatic, yet incomplete, improvement with indomethacin had nearly complete relief with verapamil monotherapy.13
  • The efficacy of sumatriptan in CPH is still controversial.14,15,16
  • Oxygen, lithium, carbamazepine, and other anticonvulsants are ineffective in patients with CPH.
  • Anesthetic blockade of the occipital nerves and supraorbital nerve have not provided significant relief. Occipital nerve blockade helps in distinguishing CPH and HC from cervicogenic headache. Supraorbital nerve blockade may help in distinguishing HC and supraorbital nerve neuralgia (in which nerve block is markedly effective).
  • Reliable evidence of efficacy of chiropractic manipulation, acupuncture, or surgical management in the treatment of CPH does not exist.

Consultations

Ophthalmologist - To evaluate ocular pathology such as glaucoma or orbital pseudotumor

Medication

Drug of choice in the treatment of CPH is indomethacin. When a patient experiences frequent unilateral headaches (ie, >4 attacks in 24 h), a drug trial with indomethacin should be considered. The dose of indomethacin should be increased to at least 150 mg/d for 3-4 d. Beneficial effect is seen usually within 48 h, but may take as long as 5 d. In one study, indomethacin effect was complete within 24 h in most patients, and frequently the effect was seen within 8 h. Maintenance dosage is usually 25-100 mg/d but may range from 12.5-300 mg/d. After discontinuation of medication, symptoms usually reappear within 12 h to a few days. However, long remission periods lasting years have been described.

About 10% of patients may experience adverse effects of indomethacin, including dyspepsia, nausea, vomiting, vertigo, gastric bleeding, purpura, and other conditions. To prevent gastric adverse effects, antacids, misoprostol, or an H2 antagonist or proton pump inhibitor may be coadministered when indomethacin is being used for longer periods. An indomethacin suppository is another option for gastric intolerance or when a higher dose (eg, 300 mg/d) is needed.

A recent article suggests that topiramate could be helpful as a preventive agent.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.


Indomethacin (Indocin)

Has absolute effect on symptoms of CPH. Available as immediate-release preparation, sustained-release preparation, suppository, and oral suspension. Ninety capsules of branded immediate-release indomethacin costs $61.38 and generic costs $25.93. Thirty capsules of sustained-release indomethacin costs $64.57 and generic costs $42.46. Recently, in one pharmacy review, cost for 30 days treatment with generic indomethacin 50 mg bid was estimated to be $5.58.

Dosing

Adult

Immediate release: 25-50 mg PO tid
Sustained release: 75 mg PO qd/bid
Suppository: 50 mg PR

Pediatric

<14 years: Not recommended except for neonates with patent ductus arteriosus
>14 years: Administer as in adults

Interactions

Concomitant use with other NSAIDs not advisable because of increased possibility of GI toxicity; diflunisal associated with serious GI hemorrhage; may reduce renal function, use caution when using medications that are excreted by kidneys; may decrease tubular secretion of methotrexate and potentiate its toxicity; like other NSAIDs, may blunt natriuretic effect of furosemide by inhibiting prostaglandin synthesis; can reduce diuretic, natriuretic, and antihypertensive effects of various other diuretic medications; probenecid may increase plasma levels; may increase serum concentration and prolong half-life of digoxin

Contraindications

Documented hypersensitivity; syndrome of nasal polyps; angioedema or bronchospastic reaction to aspirin and other NSAIDs; pulmonary hemorrhage; active GI bleeding, or history of recurrent GI lesions; simultaneous use of lithium (may result in lithium toxicity)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with renal insufficiency (ie, serum creatinine > 2 mg/dL), hepatic dysfunction, bleeding disorders (ie, platelets <75,000/mm3), parkinsonism, depression, epilepsy, psychiatric disturbances (may cause worsening of symptoms); can mask usual signs and symptoms of infection; fluid retention and peripheral edema have been reported in a few patients


Naproxen sodium (Aleve, Anaprox, Naprelan, Naprosyn)

For relief of mild to moderately severe pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in decrease of prostaglandin synthesis.

Dosing

Adult

275 mg PO tid or 550 mg bid (proper dose guidelines for CPH not established)

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Probenecid may increase toxicity; may decrease effects of loop diuretics; may increase serum lithium levels; anticoagulants may prolong PT

Contraindications

Documented hypersensitivity; peptic ulcer disease; renal or hepatic impairment; concomitant or recent use of anticoagulants; hemorrhagic conditions

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Long-term use enhances potential for adverse effects, particularly gastropathy or nephropathy


Ibuprofen (Motrin, Ibuprin)

DOC for patients with mild to moderately severe pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Dosing

Adult

400-800 mg PO q8h, not to exceed 3200 mg/d (proper dose guidelines for CPH not established)

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Probenecid may increase toxicity; may decrease effects of loop diuretics; may increase serum lithium levels; anticoagulants may prolong PT

Contraindications

Documented hypersensitivity; peptic ulcer disease; renal or hepatic impairment; concomitant or recent use of anticoagulants; hemorrhagic conditions

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Long-term use enhances potential for adverse effects, particularly gastropathy or nephropathy


Aspirin (Anacin, Ascriptin, Bayer Aspirin)

Treats mild to moderately severe pain. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Dosing

Adult

Initial dose: 900-1000 mg PO; may be repeated after 2 h if necessary (proper dose guidelines for CPH not established)

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Probenecid may increase toxicity; may decrease effects of loop diuretics; may increase serum lithium levels; anticoagulants may prolong PT

Contraindications

Documented hypersensitivity; peptic ulcer disease; renal or hepatic impairment; concomitant or recent use of anticoagulants; hemorrhagic conditions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Long-term use enhances potential for adverse effects, particularly gastropathy or nephropathy

Calcium channel blockers

These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle. Verapamil may be an effective calcium channel blocker for prophylaxis of CPH.


Verapamil (Calan, Verelan, Covera-HS)

During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle.

Dosing

Adult

Sustained release: 120 mg/d PO qd; not to exceed 480 mg/d
Immediate release: 40 mg PO tid; not to exceed 480 mg/d

Pediatric

Not established

Interactions

Carbamazepine, phenobarbital, hydantoins, vitamin D, sulfinpyrazone, and rifampin may decrease serum concentrations by increasing hepatic metabolism; amiodarone may increase toxicity; beta-blockers may increase cardiac depressant effect; cimetidine may increase serum levels; may increase serum levels of cyclosporine, theophylline, carbamazepine, and digoxin

Contraindications

Documented hypersensitivity; sinus bradycardia; cardiogenic shock; second- and third-degree heart block; sick-sinus syndrome; ventricular tachycardia; congestive heart failure; atrial fibrillation or flutter associated with accessory conduction pathways

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use caution in severe left ventricular dysfunction, hepatic or renal impairment, or hypertrophic cardiomyopathy; patients may report headache (which improves after weeks of treatment), hypotension, and dizziness

Corticosteroids

These agents may be effective in treatment of CPH. Pain relief may occur via inhibition of prostaglandin synthesis.


Prednisone (Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. High dose prescribed for first few days, followed by gradual taper.

Dosing

Adult

40-60 mg/d PO in divided doses for 5 d, followed by slow taper over 2 wk (proper dose guidelines for CPH not established); long-term use not recommended

Pediatric

Not established

Interactions

May increase digitalis toxicity secondary to hypokalemia; monitor for hypokalemia when coadministered with diuretics; phenobarbital, phenytoin, or rifampin may increase metabolism of corticosteroids, which decreases their effects; estrogens may decrease clearance; may decrease effects of salicylates

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections, fungal or tubercular skin infections; systemic fungal infections or serious infections except septic shock or tuberculous meningitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Long-term use may predispose patients to hyperglycemia, manifestations of latent diabetes mellitus, nonketotic hyperosmolar state, osteoporosis, avascular necrosis of hip, cataracts, steroid myopathy, cushingoid appearance, weight gain, suppression of pituitary-hypothalamic axis, peptic ulcer disease, suppression of growth (children), unmasking of latent infections (eg, tuberculosis, herpes zoster), increased predisposition to fungal and parasitic infections
Suppression of pituitary-hypothalamic axis may cause patients to require higher doses at times of stress
Water retention resulting from therapy may precipitate congestive heart failure; hypertension and hypokalemia may occur

Anticonvulsants

Agents with state-dependent sodium channel–blocking action and inhibitory activity of neurotransmitter GABA may have prophylactic effects on CPH.


Topiramate (Topamax)

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel–blocking action, potentiates inhibitory activity of neurotransmitter GABA. In addition, may block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy.

Dosing

Adult

25 mg PO hs; increase to 50 mg PO hs at 1 wk interval and increase further as necessary; patients with migraine will respond to 50 mg to 100 mg hs

Pediatric

Not established

Interactions

Phenytoin, carbamazepine and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels, when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants since may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of developing a kidney stone formation is increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop, can lead to glaucoma; primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia has been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures); may cause hyperchloremic, non-anion gap metabolic acidosis acute or chronic metabolic acidosis resulting in hyperventilation, and nonspecific symptoms, such as fatigue and anorexia, or more severe adverse effects including cardiac arrhythmias or stupor; chronic, untreated metabolic acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate; sprinkle capsules should be swallowed whole or carefully open capsule and sprinkle contents on soft food immediately before ingestion, do not chew or crush

Follow-up

Complications

  • Take precautions to prevent serious gastrointestinal and renal complications secondary to long-term use of indomethacin.

Prognosis

  • In the nonremitting stage of CPH, patients may need lifelong therapy, possibly with smaller doses of indomethacin.
  • Long-lasting remission periods usually reflect a nonchronic stage, but they may occur in patients with established chronic disease.
  • In chronic cases, recurrence of attacks after a drug-free period of 1.5 years has been reported.

Miscellaneous

Medicolegal Pitfalls

  • Appropriate studies should be performed to exclude secondary headache disorders.

Special Concerns

  • CPH attacks have been reported to improve during pregnancy; however, they recur after delivery.
  • Menstruation may have either a positive or negative effect on attacks.
  • Birth control pills do not seem to influence attack frequency.
  • Reliable data do not exist regarding the effects of menopause on CPH.

References

  1. Sjaastad O, Dale I. Evidence for a new (?), treatable headache entity. Headache. Jul 1974;14(2):105-8. [Medline].

  2. Sjaastad O, Dale I. A new (?) Clinical headache entity "chronic paroxysmal hemicrania" 2. Acta Neurol Scand. Aug 1976;54(2):140-59. [Medline].

  3. Russell D, Vincent M. Chronic paroxysmal hemicrania. In: The Headaches. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000:741-9.

  4. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain. Jan 1997;120 ( Pt 1):193-209. [Medline].

  5. Matharu M, May A. Functional and structural neuroimaging in trigeminal autonomic cephalalgias. Curr Pain Headache Rep. Apr 2008;12(2):132-7. [Medline].

  6. Leone M, Bussone G. Pathophysiology of trigeminal autonomic cephalalgias. Lancet Neurol. Aug 2009;8(8):755-64. [Medline].

  7. Sjaastad O, Apfelbaum R, Caskey W, et al. Chronic paroxysmal hemicrania (CPH). The clinical manifestations. A review. Ups J Med Sci Suppl. 1980;31:27-33. [Medline].

  8. Kudrow DB, Kudrow L. Successful aspirin prophylaxis in a child with chronic paroxysmal hemicrania. Headache. May 1989;29(5):280-1. [Medline].

  9. Gladstein J, Holden EW, Peralta L. Chronic paroxysmal hemicrania in a child. Headache. Oct 1994;34(9):519-20. [Medline].

  10. Broeske D, Lenn NJ, Cantos E. Chronic paroxysmal hemicrania in a young child: possible relation to ipsilateral occipital infarction. J Child Neurol. Jul 1993;8(3):235-6. [Medline].

  11. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988;8 Suppl 7:1-96. [Medline].

  12. Evers S, Bauer B, Suhr B. Cognitive processing is involved in cluster headache but not in chronic paroxysmal hemicrania. Neurology. Jul 22 1999;53(2):357-63. [Medline].

  13. Shabbir N, McAbee G. Adolescent chronic paroxysmal hemicrania responsive to verapamil monotherapy. Headache. Apr 1994;34(4):209-10. [Medline].

  14. Dahlöf C. Subcutaneous sumatriptan does not abort attacks of chronic paroxysmal hemicrania (CPH). Headache. Apr 1993;33(4):201-2. [Medline].

  15. Hannerz J, Jogestrand T. Intracranial hypertension and sumatriptan efficacy in a case of chronic paroxysmal hemicrania which became bilateral. (The mechanism of indomethacin in CPH). Headache. Jun 1993;33(6):320-3. [Medline].

  16. Pascual J, Quijano J. A case of chronic paroxysmal hemicrania responding to subcutaneous sumatriptan. J Neurol Neurosurg Psychiatry. Sep 1998;65(3):407. [Medline].

  17. Antonaci F. Chronic paroxysmal hemicrania and hemicrania continua: orbital phlebography and MRI studies. Headache. Jan 1994;34(1):32-4. [Medline].

  18. Antonaci F, Pareja JA, Caminero AB. Chronic paroxysmal hemicrania and hemicrania continua: anaesthetic blockades of pericranial nerves. Funct Neurol. Jan-Feb 1997;12(1):11-5. [Medline].

  19. Antonaci F, Pareja JA, Caminero AB. Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of sumatriptan. Headache. Mar 1998;38(3):197-200. [Medline].

  20. Antonaci F, Pareja JA, Caminero AB, Sjaastad O. Chronic paroxysmal hemicrania and hemicrania continua. Parenteral indomethacin: the 'indotest'. Headache. Feb 1998;38(2):122-8. [Medline].

  21. Bill A, Stjernschantz J, Mandahl A. Substance P: release on trigeminal nerve stimulation, effects in the eye. Acta Physiol Scand. Jul 1979;106(3):371-3. [Medline].

  22. Bogucki A, Szymanska R, Braciak W. Chronic paroxysmal hemicrania: lack of pre-chronic stage. Cephalalgia. Sep 1984;4(3):187-9. [Medline].

  23. Bordini C, Antonaci F, Stovner LJ, Schrader H, Sjaastad O. "Hemicrania continua": a clinical review. Headache. Jan 1991;31(1):20-6. [Medline].

  24. Buzzi MG, Sakas DE, Moskowitz MA. Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater. Eur J Pharmacol. Jun 20 1989;165(2-3):251-8. [Medline].

  25. Caminero AB, Pareja JA, Dobato JL. Chronic paroxysmal hemicrania-tic syndrome. Cephalalgia. Apr 1998;18(3):159-61; discussion 124. [Medline].

  26. Centonze V, Bassi A, Causarano V. Simultaneous occurrence of ipsilateral cluster headache and chronic paroxysmal hemicrania: a case report. Headache. Jan 2000;40(1):54-6. [Medline].

  27. Cohen AS, Matharu MS, Goadsby PJ. Trigeminal autonomic cephalalgias: current and future treatments. Headache. Jun 2007;47(6):969-80. [Medline].

  28. Di M, Zhu Y. [Studies on cardiac function in children aged 8-12 with simple obesity]. Chung Hua Yu Fang I Hsueh Tsa Chih. May 1995;29(3):162-4. [Medline].

  29. Di Monda V. Chronic paroxysmal hemicrania and SUNCT syndrome. Ital J Neurol Sci. Apr 1999;20(2 Suppl):S49-52. [Medline].

  30. Drummond PD. Thermographic and pupillary asymmetry in chronic paroxysmal hemicrania. A case study. Cephalalgia. Sep 1985;5(3):133-6. [Medline].

  31. Feigen LP, King LW, Ray J. Differential effects of ibuprofen and indomethacin in the regional circulation of the dog. J Pharmacol Exp Ther. Dec 1981;219(3):679-84. [Medline].

  32. Foerderreuther S, von Maydell R, Straube A. A CPH-like picture in two patients with an orbitocavernous sinus syndrome. Cephalalgia. Aug 1997;17(5):608-11. [Medline].

  33. Forderreuther S, Straube A. [A rare headache syndrome. SUNCT syndrome, hemicrania continua and red ear syndrome]. Nervenarzt. Aug 1999;70(8):754-8. [Medline].

  34. Goadsby PJ. Short-lasting primary headaches: focus on trigeminal automatic cephalgias and indomethacin-sensitive headaches. Curr Opin Neurol. Jun 1999;12(3):273-7. [Medline].

  35. Goadsby PJ, Edvinsson L. Neuropeptide changes in a case of chronic paroxysmal hemicrania--evidence for trigemino-parasympathetic activation. Cephalalgia. Oct 1996;16(6):448-50. [Medline].

  36. Hannerz J. Trigeminal neuralgia with chronic paroxysmal hemicrania: the CPH-tic syndrome. Cephalalgia. Oct 1993;13(5):361-4. [Medline].

  37. Hannerz J, Jogestrand T. Intracranial hypertension and sumatriptan efficacy in a case of chronic paroxysmal hemicrania which became bilateral. (The mechanism of indomethacin in CPH). Headache. Jun 1993;33(6):320-3. [Medline].

  38. Horven I. Dynamic tonometry. II. Methods of corneal indentation pulse registration. Acta Ophthalmol (Copenh). 1970;48(1):23-38. [Medline].

  39. Joubert J, Powell D, Djikowski J. Chronic paroxysmal hemicrania in a South African black. A case report. Cephalalgia. Sep 1987;7(3):193-6. [Medline].

  40. Kudrow L. Cluster headache: diagnosis and management. Headache. Apr 1979;19(3):142-50. [Medline].

  41. Lainez JM, Pareja Martinez AI. [Hemicrania continua]. Neurologia. Dec 1997;12 Suppl 5:50-5. [Medline].

  42. Martinez-Salio A, Porta-Etessam J, Perez-Martinez D. Case reports: chronic paroxysmal hemicrania-tic syndrome. Headache. Sep 2000;40(8):682-5. [Medline].

  43. May A, Goadsby PJ. The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab. Feb 1999;19(2):115-27. [Medline].

  44. Medina JL. Organic headaches mimicking chronic paroxysmal hemicrania. Headache. Feb 1992;32(2):73-4. [Medline].

  45. Moncada E, Graff-Radford SB. Benign indomethacin-responsive headaches presenting in the orofacial region: eight case reports. J Orofac Pain. Summer 1995;9(3):276-84. [Medline].

  46. Morales Asin F. [Chronic paroxysmal hemicrania]. Neurologia. Dec 1997;12 Suppl 5:44-9. [Medline].

  47. Moskowitz MA. Basic mechanisms in vascular headache. Neurol Clin. Nov 1990;8(4):801-15. [Medline].

  48. Newman LC, Herskovitz S, Lipton RB, et al. Chronic paroxysmal headache: two cases with cerebrovascular disease. Headache. Feb 1992;32(2):75-6. [Medline].

  49. Palmieri A, Mainardi F, Maggioni F, et al. Cluster-like headache secondary to cavernous sinus metastasis. Cephalalgia. Sep 2005;25(9):743-5. [Medline].

  50. Pareja J, Pareja J. Chronic paroxysmal hemicrania coexisting with migraine. Differential response to pharmacological treatment. Headache. Feb 1992;32(2):77-8. [Medline].

  51. Pareja JA. Chronic paroxysmal hemicrania: dissociation of the pain and autonomic features. Headache. Feb 1995;35(2):111-3. [Medline].

  52. Pollmann W, Pfaffenrath V. Chronic paroxysmal hemicrania: the first possible bilateral case. Cephalalgia. Mar 1986;6(1):55-7. [Medline].

  53. Price RW, Posner JB. Chronic paroxysmal hemicrania: a disabling headache syndrome responding to indomethacin. Ann Neurol. Feb 1978;3(2):183-4. [Medline].

  54. Quintana A, Raczka E, Giralt MT. Effects of aspirin and indomethacin on cerebral circulation in the conscious rat: evidence for a physiological role of endogenous prostaglandins. Prostaglandins. Apr 1983;25(4):549-56. [Medline].

  55. Rapoport AM, Sheftell FD, Baskin SM. Chronic paroxysmal hemicrania--case report of the second known definite occurrence in a male. Cephalalgia. Jun 1981;1(2):67-9. [Medline].

  56. Raskin NH. Short-lived head pains. Neurol Clin. Feb 1997;15(1):143-52. [Medline].

  57. Raskin NH, Schwartz RK. Icepick-like pain. Neurology. Feb 1980;30(2):203-5. [Medline].

  58. Rozen TD. LASH: a syndrome of long-lasting autonomic symptoms with hemicrania (A new indomethacin- responsive headache). Headache. Jun 2000;40(6):483-6. [Medline].

  59. Russell D. Chronic paroxysmal hemicrania: severity, duration and time of occurrence of attacks. Cephalalgia. Mar 1984;4(1):53-6. [Medline].

  60. Saunte C. Chronic paroxysmal hemicrania: salivation, tearing and nasal secretion. Cephalalgia. Mar 1984;4(1):25-32. [Medline].

  61. Saunte C, Russell D, Sjaastad O. Chronic paroxysmal hemicrania. IX. On the mechanism of attack-related sweating. Cephalalgia. Sep 1983;3(3):191-9. [Medline].

  62. Sawrasewicz-Rybak M. [Chronic paroxysmal hemicrania]. Wiad Lek. 1999;52(1-2):56-60. [Medline].

  63. Sjaastad O. Chronic paroxysmal hemicrania. In: Sjaastad O, ed. Cluster Headache Syndrome. 1992. London: WB Saunders; 291-92.

  64. Sjaastad O. Chronic paroxysmal hemicrania. In: Vinken PI, Bruyn OW, Klawans HL, et al, eds. Handbook of Clinical Neurology. 48. Amsterdam: Elsevier; 1986:257-66.

  65. Sjaastad O, Antonaci F. A piroxicam derivative partly effective in chronic paroxysmal hemicrania and hemicrania continua. Headache. Oct 1995;35(9):549-50. [Medline].

  66. Sjaastad O, Kruszewski P. Trigeminal neuralgia and "SUNCT" syndrome: similarities and differences in the clinical pictures. An overview. Funct Neurol. Mar-Apr 1992;7(2):103-7. [Medline].

  67. Sjaastad O, Russell D, Saunte C, et al. Chronic paroxysmal hemicrania. VI. Precipitation of attacks. Further studies on the precipitation mechanism. Cephalalgia. Dec 1982;2(4):211-4. [Medline].

  68. Sjaastad O, Saunte C, Graham JR. Chronic paroxysmal hemicrania. VII. Mechanical precipitation of attacks: new cases and localization of trigger points. Cephalalgia. Jun 1984;4(2):113-8. [Medline].

  69. Sjaastad O, Saunte C, Russell D. Cluster headache. The sweating pattern during spontaneous attacks. Cephalalgia. Dec 1981;1(4):233-44. [Medline].

  70. Sjaastad O, Saunte C, Salvesen R. Shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhea. Cephalalgia. Jun 1989;9(2):147-56. [Medline].

  71. Sjaastad O, Spierings EL. "Hemicrania continua": another headache absolutely responsive to indomethacin. Cephalalgia. Mar 1984;4(1):65-70. [Medline].

  72. Sjaastad O, Spierings EL, Saunte C. "Hemicrania continua". An indomethacin responsive headache. II. Autonomic function studies. Cephalalgia. Dec 1984;4(4):265-73. [Medline].

  73. Sjaastad O, Stovner LJ, Stolt-Nielsen A. CPH and hemicrania continua: requirements of high indomethacin dosages-- an ominous sign?. Headache. Jun 1995;35(6):363-7. [Medline].

  74. Souza Souza Carvalho D, Salvesen R, Sand T, et al. Chronic paroxysmal hemicrania. XIII. The pupillometric pattern. Cephalalgia. Sep 1988;8(3):219-26. [Medline].

  75. Stein HJ, Rogado AZ. Headache rounds. Chronic paroxysmal hemicrania: two new patients. Headache. Mar 1980;20(2):72-6. [Medline].

  76. Tehindrazanarivelo AD, Visy JM, Bousser MG. Ipsilateral cluster headache and chronic paroxysmal hemicrania: two case reports. Cephalalgia. Oct 1992;12(5):318-20. [Medline].

  77. Vijayan N. Symptomatic chronic paroxysmal hemicrania. Cephalalgia. Apr 1992;12(2):111-3. [Medline].

  78. Wennmalm A, Carlsson I, Edlund A, et al. Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man. Arch Toxicol Suppl. 1984;7:350-9. [Medline].

  79. Zukerman E, Peres MF, Kaup AO. Chronic paroxysmal hemicrania-tic syndrome. Neurology. Apr 11 2000;54(7):1524-6. [Medline].

Keywords

Sjaastad syndrome, IHS code: 3.2 chronic paroxysmal hemicrania, ICD-9 code: 346.9 hemicrania, CPH, headache, indomethacin, chronic paroxysmal hemicrania, unilateral headache, headaches with autonomic activation, headaches without autonomic activation, chronic and episodic paroxysmal hemicrania, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing, SUNCT syndrome

Contributor Information and Disclosures

Author

Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Manish K Singh, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American Association of Physicians of Indian Origin, American Headache Society, American Medical Association, and American Society of Regional Anesthesia and Pain Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Jashvant Patel, MD, Medical Director, Department of Pain Medicine and Comprehensive Rehabilitation, Medical College of Pennsylvania Hahnemann University
Jashvant Patel, MD is a member of the following medical societies: Alberta Medical Association, American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Society of Regional Anesthesia and Pain Medicine, and Medical Society of the State of New York
Disclosure: Nothing to disclose.

Medical Editor

Jorge E Mendizabal, MD, Consulting Staff, Corpus Christi Neurology
Jorge E Mendizabal, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, National Stroke Association, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

James H Halsey, MD, Professor, Department of Neurology, University of Alabama Medical Center
James H Halsey, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neuroimaging, Medical Association of the State of Alabama, New York Academy of Sciences, Pan American Medical Association, Sigma Xi, Society for Neuroscience, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

Further Reading

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)