10.0: Headache associated with metabolic disorder

There are a variety of types of headache that may be associated with different derangements of metabolism. This subject is only covered briefly in this chapter and the interested reader is referred to other more extensive headache texts such as Dalessio (1993) and Raskin (1988).

10.1: Hypoxia

 Headache Associated with Hypoxia

Dalessio (1993) points out that experimentally induced cerebral hypoxemia, (Wolff and Lennox, 1930), especially when coupled with an increase in carbon dioxide tension in the blood, results in extreme dilatation of cerebral vessels, notably of the arteries and arterioles. This observation is probably related to the fact that some persons at high altitudes (Bancroft et al., 1922; Monge, 1942) complain of headache that persists for hours or days until physiologic adjustments have been achieved, or until the individual returns to a lower altitude. Such headaches are usually prevented by ingestion of acetazolamide prior to ascent to high altitude. Associated with the intense throbbing headache is a sensation of fullness of the head, hot flushes of the face, photophobia, injection of the ocular mucosa, and deep cyanosis. It is likely that such headaches are due to cerebrovascular distention.

There are a variety of specific situations in which headache may occur from hypoxia alone or from hypoxia and hypercapnia together, as described below.

Decompression Headache

Arterial hypoxia, not contaminated by hypercapnia, occurs in those exposed to high altitudes and in those in decompression chambers. Decompression sickness appears when a sudden change in the pressure of ambient gases, to which the subject has become equilibrated, occurs. A sudden reduction in pressure of 45% is usually sufficient to cause symptoms.

The symptoms produced by rapid decompression are caused primarily by the formation of nitrogen gas bubbles in blood and fatty tissues. Nitrogen does not diffuse readily and is not used in body metabolism. When body fluids and tissues saturated with nitrogen are suddenly exposed to a lower pressure, bubbles of nitrogen gas form that lodge in small blood vessels and fatty tissues, because nitrogen is five times more soluble in oil than in water (Behnke, 1965).

Most decompression sickness now occurs in sports divers (Dalessio, 1993). The neurologic complications can be striking (Erde and Edmonds, 1975; Kidd and Elliott, 1975). Both the spinal cord and brain are affected. Bilateral throbbing headache occurs frequently and at times may be the only symptom of decompression sickness. The headache can be indistinguishable from migraine without aura. A migraine attack after decompression may require recompression therapy, as the headache itself is indistinguishable from that produced by arterial gas embolism to the brain.

Treatments for both high-altitude and decompression sickness are generally preventive. Descent from altitude will abolish some manifestations but may only retard others. Thus, aviators who have experienced decompression sickness should not be re-exposed even to low altitudes of flight for 72 to 96 hours, since re-expansion of nitrogen bubbles already present in fatty tissues may exacerbate their signs and symptoms (Dalessio, 1993).

Adequate recompression therapy is the only specific treatment for decompression sickness. At times this may require prolonged recompression, for more than several days. All other measures can be considered as ancillary, including the use of 100% oxygen and methods to retard or prevent brain edema (dexamethasone, 8 to 10 mg every 4 to 6 hours, and intravenous injection of mannitol or dextran).

Headache Associated with High Altitude

Theses headache occur within 24 hours after sudden assent to altitudes above 3000 meters and, according to IHS coding criteria, are associated with at least one or other symptoms typical of high altitude, namely: Cheyne Stokes respirations at night, desire to overbreath, and dyspnea.

Appenzeller (1972) pointed out that headache may be associated with acute mountain sickness, acute pulmonary edema of altitude, and chronic mountain sickness in well-acclimatized subjects. Altitude headache is uncommon below 8,000 feet, appears with increasing frequency at higher elevations, and above 12,0000 feet is more or less universal in persons not acclimatized to altitude.


10.2: Hypercapnia

Retention of CO2 causes vasodilatation and diffuse headache. Chronic hypercapnia from pulmonary disease and situations such as the Pickwickian syndrome are often accompanied by increased intracranial pressure and severe diffuse headache similar to that seen in pseudotumor cerebri. The diagnostic criteria are that there is an arterial pCO2 increased above 50 mm Hg in the absence of hypoxia.

10.3: Mixed hypoxia and hypercapnia

This type of headache is often seen in pulmonary patients such as those alluded to below in which there is a combination of hypoxia and hypercapnia as in the Pickwickian syndrome. In this syndrome, obese person usually with accompanying pulmonary disease, develop chronic hypoxia and hypercapnia. Papilledema and severe headache are often accompaniments.

10.4: Hypoglycemia

Headaches may be precipitated by attacks of hunger and by fasting. Precipitation of migraine by hunger (Blau and Cummings, 1966) led to several studies of carbohydrate metabolism. Although headache is a common symptom of insulin-induced hypoglycemia (Hockaday, 1975), it clearly is not hypoglycemia per se that is responsible for the precipitation of migrainous attacks by hunger (Pearce, 1971). The lowest blood glucose levels recorded during fasting in subjects experiencing an attack are not different from those in subjects who do not develop headache (Hockaday et al, 1971).

During extended standard insulin hypoglycemia tests, migrainous subjects demonstrate hypoglycemia unresponsiveness (Rao and Pearce, 1971). Since the cortisol response to insulin-induced hypoglycemia and the metapyrone test is normal in migraineurs, a defect of the hypothalamic-pituitary-adrenal axis is not likely to be contributory. A diminished hyperglycemic response to glucagon (DeSilva et al, 1974) is consistent with an impairment in the hepatic mobilization of glucose. During migraine attacks, decreased glucose tolerance, low plasma insulin levels, an elevations of free fatty acids (Anthony, 1986), glycerol, ketone bodies, secretin (McLoughlin et al, 1978), and growth hormone (Shaw et al, 1977) are noted. These findings (Table 36.2) taken together, are consistent with a chronic stress reaction with heightened sympathetic activity (Taggart et al, 1973). Fasting results in increased turnover of brain serotonin (Curzon et al, 1972), which may be important to the mechanism of headache provoked by hunger.

10.5: Dialysis

Headache occurs with varying degrees of severity during dialysis in about 70 percent of dialyzed patients (Raskin, 1988). The most common form of "dialysis headache" is the precipitation of migraine headaches in those with preexisting migraine. Other patients without previous headache disorders experience headache only in association with dialysis, usually during the third or fourth hour. It is usually reported as bilateral and throbbing without focal neurologic symptoms (Bana et al, 1972). Headaches may disappear after nephrectomy or after a successful transplant. Later, if the transplant is subsequently rejected, headaches may reappear as a symptom of rejection continuing until nephrectomy is carried out (Graham, 1976). There is some evidence that arterial renin and 18-hydroxy-11-deoxycorticosterone levels, obtained during hemodialysis, are lower in patients who are subject to headache (Graham, 1976; Bana et al, 1972; Bana and Graham, 1978). However, the preponderance of evidence points to shifts of water into the brain as the major cause of "disequilibrium," the term denoting a conglomeration of symptoms, including headache, that occur during or after dialysis (Arieff et al, 1978).

Quoting from Raskin (1988), "The mechanism of these symptoms was originally believed to be the lag in the reduction of brain urea compared to blood urea because of the influence of the blood-brain barrier. This effect was thought to produce an osmotic gradient between blood and brain, resulting in movement of water into brain, leading to cerebral edema, increased intracranial pressure, and symptoms of encephalopathy. This hypothesis became known as the reverse urea effect; the unequal effects of dialysis upon tissue and blood solutes, resulting in an osmotic gradient, underlies the naming of this disorder the disequilibrium syndrome. Experimental models of disequilibrium support the hypothesis that osmotically active substances are ("idiogenic osmoles") are present in brain in the dialyzed uremic animal (and not in the dialyzed nonuremic animal), creating an osmotic gradient between brain and blood that results in shifts of water into brain (Raskin and Fishman, 1976). The nature of the idiogenic osmoles is not clear, but they must play a role because the amount of urea transiently retained in the brain is not sufficient to account for cerebral edema, nor are alterations in brain or plasma sodium likely to underlie disequilibrium. The marked lowering in cerebrospinal fluid (CSF) pH that occurs in dialyzed uremic animals may reflect the cerebral accumulation of organic acids, and such osmotically active solutes may also be important to the genesis of the neurologic disturbances that occur associated with hemodialysis."

10.6: Headache related to other metabolic abnormality

Adrenal Dysfunction

Raskin (1988) reported a patient with lifelong migraine who had worsening of her headache attacks concurrent with involvement of Conn’s syndrome. Following subtotal adrenalectomy her migraine attacks ceased (Stanford and Greene, 1970). Similarly, Cushing’s syndrome and the hypoadrenal state following steroid withdrawal may be the source of de novo headaches that resemble migraine (Graham, 1976). Headache is a complaint of over 40 percent of patients with Cushing’s syndrome (Ross and Linch, 1982). The secretion of many pituitary-derived hormones, including ACTH, is influenced by central serotonergic mechanisms, as is aldosterone secretion (Shenker et al, 1985).

According to Glueck and Bates (1986), migraine occurs with higher than chance frequency among patients with hyperlipidemias and dyslipoproteinemias. Restoration of serum lipids to normal levels with clofibrate dramatically improved the headache problem in a well-studied patient (Leviton and Camenga, 1969). However, the treatment of dyslipoproteinemias in large populations of patients does not appear to reduce the frequency and severity of headaches (Leviton, 1986). Whether the alteration in serum viscosity that accompanies hyperlipidemia is important to the trigger mechanism of headache is not clear.
 

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