There are some rare medical causes of headache which are easily missed. The following is a partial list of potentially serious causes of headache we have seen in the Headache Clinic. These medical problems are so rare that their existence may not be suspected.
Among the large number of patients we evaluate, a very few will have undetected chronic infection of the coverings surrounding the brain, such as tuberculosis, aids, or fungal infections. Headaches can also be caused by increased spinal fluid pressure which cannot be detected by a cranial MRI. We have seen low spinal fluid pressure cause headaches as well.
There are headache types which respond only to the medicine indomethacin such as hemicrania continua; migraine variants requiring specific management such as cluster headache; inflammatory disorders (some of which can be medical emergencies which may cause blindness) such as temporal arteritis, and a condition called systemic lupus erythematosis with anticardiolipin antibodies which may cause stroke as well as headache.
In North Carolina we see Rocky Mountain Spotted Fever. Lyme disease, chronic mononucleosis, and other undetected systemic infections may present with headache. We also see toxic disorders such as carbon monoxide, mold, and other environmental poisoning.
We have also seen genetic diseases where headache is associated with an increased risk for stroke, such as blood clotting disorders and Cadasil syndrome; congenital malformations associated with headache and also risk for other diseases, such as patent foramen ovale (a hidden hole in the heart wall which sometimes requires a special "bubble study" cardiac ultrasound to detect) and Marfan’s syndrome (tall people with arm span greater than their height, who may die early in life from sudden rupture of a weakened aorta unless diagnosed and treated).
While most brain tumors and other masses in the brain are easily detected by CT or MRI, rare infiltrative tumors of the brain such as lymphoma, and more common very small tumors of the pituitary, may cause headaches without changes on MRI. Brain aneurysms may require special studies to detect.
Hormonal problems are commonly associated with onset of new headaches. The patient with a hormonal problem will sometimes have headache as the primary symptom. Women often already know that they have a hormonal problem underlying their headache. Besides imbalances in estrogen/progesterone/testosterone, we see other hormonal problems causing headache, such as thyroid, adrenal, growth hormone, or parathyroid dysfunction.
We also see sleep disorders such as sleep apnea which may typically cause a morning headache, but if not detected and treated may cause hypertension and heart failure over time. Almost all of the problems above will "have a negative MRI", and so the "hidden disease’ may be missed.
Sometimes, patients receive an MRI to investigate headache, but the MRI is not done in a way that will detect the problem. In some headache conditions it is necessary to administer a contrast agent (gadolinium) by IV to detect such conditions as low pressure headache or cancer of the meninges. In other cases, specific enlarged MRI views of the pituitary with contrast are necessary to detect a pituitary tumor. In others, clotting of the veins in the brain or inflammation of the arteries can only be detected by an MRI arteriogram or venous angiogram. So, a "negative MRI’ can be misleading. You have to consider what type of MRI was done and whether IV contrast was given.
When a person who was previously well is diagnosed with two or even more different illnesses in a short period of time, the likelihood of an unusual or missed diagnosis is increased. So for example, you are told by a family doctor that you have chronic fatigue, by an ENT doctor that you have vertigo, and by a neurologist that you have migraines- and two years ago you were well.
If you have two or more of the following in addition to having headaches not responding to treatment, consider further investigation: worsening with treatment; fibromyalgia, insomnia, depression, anxiety, chronic sinus problems, chronic fatigue; back or neck pain; irritable bowel syndrome; unexplained heart rhythm problems; and dizziness or unexplained vertigo which does not respond to treatment.
Can medicines cause disease? Of course, some serious ones. Although extremely rare, some happen quite rapidly, such as liver failure or bleeding with Depakote (an anticonvulsant sometimes used to treat migraine) and kidney stones or a rare type of glaucoma with Topamax. Beta blockers (Inderal and Toprol) and antidepressants can cause sexual dysfunction or loss of interest in sex. Almost all medications for headache can cause sedation and put the patient at risk for automobile accidents.
We have seen patients on antidepressants and antinausea medications such as Reglan (metaclopromide) have severe psychiatric reactions such as suicidal feelings or sudden urges to self injury. Rarely, allergic and anaphylactic deaths occur with aspirin and other pain medications. There is an extremely small heart attack risk in patients with undetected heart disease who take Imitrex or one of the other triptans.
These emergency side effect problems, in general, are extremely rare. It is much more common, in our experience, for long term side effects to go undetected.
The most common "hidden disease" caused by medication is weight gain. Depakote (sodium valproate) and Elavil (amitriptyline) commonly produce this side effect. It is important to consider the history of cardiac risk factors in the patient and in the family before using such agents. This is just as important in the twenty year old as the fifty year old. The issue is the risk of heart attack and stroke many years from now. Weight gain is a serious, frequent, and often unnecessary, side effect of headache treatment, and every effort should be made to prevent it.
Another very common "hidden disease" caused by medication is high blood pressure. Recently, cardiology consensus has moved to a much lower standard for what is considered a "safe" blood pressure for the long term. The trouble here is that many of the antidepressants used to treat headache raise blood pressure. Those antidepressants most beneficial for headache all have an effect of increasing norepinephrine, a brain neurotransmitter which is directly related to modulation of pain. Unfortunately, metabolism of norepinephrine to adrenaline may raise blood pressure as well. So using some types of antidepressants for pain may cause elevation of blood pressure.
Effexor (venlafaxine), Elavil (amitriptyline), and Pamelor (nortriptyline) very commonly have these side effects. Since the new blood pressure recommendations are so low, even a small increase in blood pressure caused by medication may put a patient into the "prehypertension" category. For a young patient facing years of medication, this is a serious matter. Compounding the problem is that checkups for the kinds of problems these medications are prescribed for (headache, pain disorders, depression, insomnia) may not include charting of blood pressure. Changes in blood pressure may be very subtle, a matter of ten points or so- but even a small increase in blood pressure may translate into long-term cardiovascular risk.
Another long term "silent disease" caused by medication is osteoporosis, a leading cause of disability and suffering in the elderly. Osteoporosis may also cause "dowager’s hump" in middle aged women. Many patients are already aware of the importance of taking calcium supplements and exercising throughout their lifetime to help prevent osteoporosis. Very few realize, however, that some headache medicines can cause osteoporosis. Topamax, for example, was known to sometimes cause significant metabolic acidosis and thus, fatigue, when the drug was first approved for use by the FDA. Based on the effect of acidification of the urine, however, we were quite curious as to whether there would be an effect of Topamax on bone formation. It turns out that bone density measurements have not been well studied in patients taking Topamax.
It is almost certainly the case that even mild metabolic acidosis from Topamax (topiramate) is a risk for bone loss and osteoporosis over years. Topamax is a very effective medication for migraine; but the potential side effects should be monitored and prevented by calcium supplements and a wellness exercise program, measurement of the serum chloride for detection of acidosis, and correction with sodium bicarbonate if acidosis is present and the medication is going to be continued. If the long term administration of Topamax is necessary, we recommend directly measuring bone density to make sure their wellness program is working and that bones are getting stronger rather than weaker over time.
Emergency Causes of Headache
Meningitis- fever, stiff neck
Encephalitis- confusion, fever.
Brain tumor- weakness on one side, persistent visual change
Brain Hemorrhage- sudden explosive headache
Aneurysm- headache with straining or bending over
Undetected Medical Illness- headache that won’t go away
