8.0: Headache associated with substances or their withdrawal

The IHS Classification (Olesen, 1988) comments that worsening of pre-existing headache should be coded according to the pre-existing headache form. Patients who develop a new form of headache (including migraine, tension-type headache, or cluster headache) in close temporal relation to substance use or substance withdrawal is specified and the criteria listed below are coded to this group 8.

8.1: Headache induced by acute substance use or exposure

It is important to establish that a substance really induces a headache. Double-blind placebo controlled experiments are necessary, therefore, as commented on by Olesen (1988). Two studies of patients who reported headache after dark chocolate or aspartame had controlled trials and it was found that headache was equally frequent after placebo. The diagnostic criteria for headache induced by acute substance abuse or exposure is as follows:

A. Occurs within a specified time after substance intake.

B. A certain required minimum dose should be indicated.

C. Has occurred in at least ½ of exposures and at least 3 times.

D. Disappears when substance is eliminated or within a specified time thereafter.

There are a variety of substances and particular foods that may precipitate vascular headache. Alcohol beverages commonly provoke headache in individuals who are susceptible to foods or beverages. Headache usually appears within 30 to 45 minutes after alcohol consumption correlating with the peak blood alcohol levels and the time required for alcohol to dilate skin arterioles so that intra- or extracranial vasodilatation id not likely to be the mechanism underlying headache (Raskin, 1988).

Other substances producing headache include nitroglycerin. Nitroglycerin (NTG) is a fundamental compound of dynamite and was eventually implicated as the cause (Schwartz, 1946) of headache among factory workers in plants manufacturing explosives. Headache accompanies the administration of 0.3 or 0.4 mg of NTG when used for angina pectoris in over 50 percent of patients. It usually stops after 3 to 10 days of continued use. Workers in munitions plants also acquire a tolerance to NTG, but it can rapidly be lost over the weekend. To prevent Monday morning headaches, workers have been known to rub NTG into their skin or use impregnated hat sweatbands on weekends (Cowan, 1986). Niacin used to lower cholesterol often produces acute vasodilation in severe generalized throbbing headache.

Common foods capable of inducing headache in susceptible patients include alcoholic beverages, citrus fruits, chocolate, and dairy products (Peatfield et al, 1984; Hanington and Harper, 1968). There is not specific evidence that this is actually an allergic phenomenon. Some evidence implicates tyramine and phenylethylamine, which occur principally in cheese and chocolate. Other headache-inducing chemicals in food identified to date include sodium chloride (Brainard, 1976; 1981), sodium nitrate (Henderson and Raskin, 1972), monosodium glutamate (Schaumburg et al, 1969), and aspartame (Johns, 1986).


Hot dog headache

In the IHS Classification, this is known as nitrate/nitrite induced headache. Raskin and his associates have described an entity termed "hot dog headache." As he points out (1988) many patients experience various degrees of headache shortly after eating frankfurters or other cured meat products. The evidence implicates the nitrite content of these foodstuffs as the cause of headache. Similar to NTG-induced headaches, they are usually bitemporal or frontal, pulsatile about half the time, and are sometimes accompanied by facial flushing. Patients experiencing these symptoms are sensitive to as little as 1 mg sodium nitrite (Henderson and Raskin, 1972), a dose that is hardly likely to exert direct effects upon arterial walls (Crandill et al, 1931). The observation that nitrite impurities in rock salt caused red patches in cured meat led to the deliberate use of fixed concentrations of salt and nitrite to produce a more uniformly colored product.

The coloring agent was not sodium nitrate, but sodium nitrite, which is formed in meat by the bacterial and chemical reduction of nitrate; nitrites have been generally substituted for nitrates in the curing process. Nitrite and its decomposition product, nitric oxide, react with myoglobin and hemoglobin to form the red compounds, nitrosomyoglobin and nitrosohemoglobin (Halliday, 1967). Human endogenous synthesis of nitrate occurs de novo and is increased by the ingestion of nitrite (Lee et al, 1986). Government regulations limit the nitrite levels reached during the treatment of cured meats to 200 ppm (200 mg/kg meat); cooking and storage lead to a reduction in the nitrite concentration so that the nitrite concentration of cured meat is 50 to 130 mg/kg.

Chinese Restaurant Syndrome

This is also known as monosodium glutamate induced headache (IHS classification 8.1.2.). Reif-Lehrer (1977) reports that up to 30 percent of people who eat Chinese food report adverse reactions (Kerr et al, 1977). Headache and tightness around the face are the most commonly reported symptoms, and may also report dizziness, diarrhea, nausea, and abdominal cramps; these symptoms constitute the "Chinese restaurant syndrome." Monosodium glutamate (MSG), the chemical precipitant of these symptoms (Schaumberg et al, 1969) is one of the active ingredients in soy sauce and is used as a food additive for its flavor-enhancing properties more by some Chinese chefs than others. When injected intravenously, MSG produces a stereotyped sequence of symptoms that begins with a burning sensation of the chest that then spreads to the neck, shoulders, upper limbs, and abdomen. This is followed by a sensation of pressure over the chest and finally by tightness and pressure over the face. Three placebo-controlled studies have shown that orally administered MSG will provoke a variety of symptoms in about one-third of the text population (Kenney and Tidball, 1972; Kenney, 1979).

Vitamin-A-Induced Headache

Raskin (1988) notes that there is both an acute severe headache from major exposure to vitamin A and the chronic headache that occurs in increased intracranial pressure. It has been known that violent headaches may result from the ingestion of large quantities of vitamin A ever since Rodahl and Moore (1943) found that polar bear liver contains approximately 15,000 I.U. vitamin A per gram, thus identifying the agent responsible for the illness describe by Arctic explorers over 100 years ago.

Headache is the dominant syndrome of acute hypervitaminosis A; it is often violent and located frontally and retro-orbitally. Nausea, abdominal pain, vertigo, and sluggishness often accompany headache, and usually appear 4 to 8 hours after ingestion of vitamin A. Two million units of vitamin A in a single dose given to four adults produced dull headaches in all four and no other symptoms (Gerber et al, 1954). Chronic hypervitaminosis A has been reported in patients who have ingested at least 15,000 I.U. of vitamin A daily for weeks to months; the principal symptoms are joint pain, fatigue, alopecia, fisuring of the lips, hepatomegaly, and headache (Stimson, 1961). Children more often than adults may develop increased intracranial pressure as a manifestion of vitamin A intoxication (Muenter et al, 1971).

The total plasma vitamin A level may be normal in patients with unequivocal chronic hypervitaminosis A (Smith and Goodman, 1976). This observation underlines the importance of inquiring about patients’ vitamin intakes to explain their symptoms. Over a 10-year period, nine patients have been encountered who reported daily bifrontal or bitemporal pulsating headache; their symptoms began days to weeks after 25,000 I.U. of vitamin A ingestion was initiated on a daily basis. In all 15 patient, plasma vitamin A levels were in the normal range; headache completely subsided several days to weeks after vitamin A intake ceased (Raskin, unpublished observations--cited in Raskin, 1988).



8.2: Headache induced by chronic substance abuse or exposure

The diagnostic criteria (IHS, Olesen, 1988) for such headaches are as follows:

A. Occurs after daily doses of a substance for > 3 months.

B. A certain required minimum dose should be indicated.

C. Headache is chronic (15 days or more a month).

D. Headache disappears within 1 month after withdrawal of the substance.

So far, headache induced by chronic use of ergotamine and analgesics has only been described when the drugs have been taken for a headache disorder, not when they have been taken for other disorders. In this category are included categories such as 8.2.1, ergotamine induced headache, with the diagnosis only being allowed to be made after withdrawal of ergotamine resulting in relief from ergotamine induced headache. The category 8.2.2 is analgesics abuse headache and includes one or more of the following: 1) > 50 g of aspirin a month or equivalent of other mild analgesics, 2) > 100 tablets a month of analgesics combined with barbiturates or other non-narcotic compounds, and 3) one or more narcotic analgesics. This diagnosis can only be made after withdrawal of substances resulting in relief of substance induced headache (but usually not from the primary headache).

Chronic exposure to low levels of carbon monoxide from faulty heaters is a cause of severe headache and this may be true of a variety of chemicals. Some of the acute headaches upon exposure to agents such as nitroglycerin or MSG were discussed above. It is believed that such people have lower thresholds than the average person which renders them susceptible to headaches under those conditions as well. However chronic exposure to many of these chemicals in lower doses such as nitroglycerin will produce headaches.

8.3: Headache from substance withdrawal (acute use)

Headaches associated with chemical toxins, systemic infections and metabolic disorders, the so-called toxic vascular headaches are well reviewed by Meyer and Dalessio (1993). A number of systemic conditions are associated with bilateral and symmetrical, throbbing headache. It is likely that the headaches reflect painful dilatation of cerebral and scalp blood vessels.

"Hangover" headache

Dalessio (1993) points out that there is a body of evidence that hangover headaches resulting from excessive alcohol ingestion belongs in the category of toxic vascular headache. Cerebral blood flow is increased during acute alcoholic intoxication, however the mechanism of the following headache, usually the morning after the ingestion, is complex. Impurities in alcoholic beverages also have significant pharmadynamic effects, but it is hard to precisely define their role in hangover headache. There may be a vasodilatation after the alcohol withdrawal. Alcohol is also well-known as a precipitator of migraine and cluster headache, possibly because of increased prostacycline synthesis in aspirin, endomethacine, and other antisteriodal and anti-inflammatory agents, all of which are potent cerebrovasive constrictors, usually lessening hangover headaches.

  Post seizure headaches

Headache following a generalized seizure with loss of consciousness is usually generalized, moderately intense, throbbing, and with several hours duration. Once again, it is believed that there is widespread postectovasodilitation of cerebral vessels. Similar mechanisms may explain the headache associated with hypoxia and ischemic hypoxia (Dalessio, 1993).

  Headache Associated with Infection or Fever

Septicemia, bacteremia, and fever are commonly associated with headache. It is unlikely, however, that the agent responsible for the fever is identical to that resulting in the headache. The most intense, prolonged headaches associated with infections are those that accompany typhoid fever, typhus fever, and influenza. The headache is dull, deep, aching, and generalized, but is often worse, especially at the beginning, in the back of the head. It is increased in intensity by bodily effort. It is often worse in the latter part of the day, especially if the patient is ambulatory, or when the patient is most exhausted or prostrated. The intensity of pain is decreased by manual compression of the common carotid artery. It is not modified appreciably by ergotamine tartrate, except possibly toward the end of the period of the headache.

Headache Caused by Chemical Agents, with and without Anemic Cerebral Vasodilation

Chief among these headaches are those caused by carbon monoxide. Acetanilid, when used in excess, may cause headache by converting hemoglobin to methemoglobin , with resultant hypoxemia. In addition to the methemoglobinemia and sulfhemoglobinemia such as follows the ingestion of nitrates, sulfonamides, aniline compounds, acetanilid, and phenacetin are those headaches that occur in the acute stage of poisoning from ethyl alcohol, carbon tetrachloride, benzene, arsenic, lead, anticholinesterase, insecticides, and the nitrates, including nitroglycerin. Apresoline, thorazine, and a calcium channel blockers, by virtue of their vasodilating action, may produce headache in some patients. Withdrawal of cerebral active drugs such as ergotamine, amphetamine, caffeine, and methysergide from those who have been using them in excess for long periods may precipitate severe headache. A common situation in patients with chronic cluster and migraine headaches is habitual use of ergotamine with resulting ergotamine withdrawal headaches when the drug is discontinued. This results in a vicious cycle of daily headaches, which is best treated by total withdrawal of ergotamine.

8.4: Headache from substance withdrawal (chronic use)

This category includes withdrawal from chronic ergotamine use and from caffeine. Specific diagnostic criteria are set up as described by the IHS (Olesen, 1988). For ergotamine withdrawal headache, the criteria include that it is preceded by daily ergotamine intake of > 2 mg of oral ergotamine or 1 mg of rectal ergotamine, and that it occurs within 48 hours after withdrawal of ergotamine.

Caffeine Withdrawal Headache (IHS category 8.4.2)

The diagnostic criteria for this type of headache are the following:

A. The patient has consumed caffeine daily and > 15 g per month.

B. Occurs within 24 hours after last caffeine intake.

C. Is relieved within one hour by 100 mg of caffeine.

Pharmacologically, caffeine is a cerebral vasoconstrictor, and withdrawal presumably results in excessive cerebral vasodilation and vascular congestion (Dalessio, 1993). In studies of two subjects, caffeine withdrawal headache has been shown to have many features suggesting that the pain arises from distention of intracranial, and possibly extracranial arteries. Withdrawal from caffeine may be also responsible for the headaches that follow chronic Cafergot use, thereby having and dual withdrawal headache both from Ergonovene Tartrate and caffeine the two ingredients of Cafergot. There are other substances used chronically which may precipitate vasodilatation and subsequent vascular headache upon withdrawal.

8.5: Headache associated with substances but with uncertain mechanism

In this category the IHS includes birth control pills or estrogen (category 8.5.1). It is believed at this point that the literature is conflicting and more study is needed. However, most people who treat vascular headaches are convinced that the use of birth control pills or estrogen exacerbates pre-existing migraine. Of note is the fact that most women migraineurs have a dramatic cessation or decrease in their headaches during pregnancy.
 

 

 

Return to Other Headaches