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Keywords:

  • zolmitriptan;
  • spinal cord infarction

Abstract

  1. Top of page
  2. Abstract
  3. CASE HISTORY
  4. COMMENTS
  5. REFERENCES

A 50-year-old woman with a history of migraine without aura, predominantly occurring around her menstrual periods, developed a spinal cord lesion following the use of zolmitriptan. The partial lesion of the cord at T7 predominantly involved the spinothalamic pathways on the left side. Clinical features suggested that the lesion was an ischemic infarct, and this was confirmed by an MRI scan. There were no other known risk factors for vascular disease. There has been mild improvement of her symptoms, but most of the symptoms did not resolve. There are isolated case reports of stroke secondary to the use of triptans, however, this is the first case of spinal cord infarction reported following the use of this group of drugs. The temporal relationship suggests that the spinal cord infarction may be related to the use of zolmitriptan.

Since the introduction of sumatriptan for the acute treatment of migraine headache, several other triptans have been developed and marketed. This has revolutionized the treatment of migraine and has also broadened our understanding of the basic pathophysiology of migraine. These drugs are specific agonists of 5-HT/lB/lD receptors. The major concern with the use of these drugs has been the potential for vasoconstriction, especially of the coronary vessels. Indeed, there are several reports in the literature of patients developing myocardial infarctions or cardiac arrhythmia with fatal outcome in a very small number of patients. 1–6 Reports of such serious complications have been very few considering the widespread use of these drugs. The majority of these complications occurred in patients in whom there was preexisting coronary artery disease that was not recognized. Once this potential complication was identified and widely publicized, the occurrence of such complications declined dramatically.

There are also rare reports of neurological complications possibly related to the use of triptans. We wish to report the case of a patient with no known risk factors for vascular disease who developed ischemic infarction of the spinal cord while using zolmitriptan for the treatment of menstrual migraine.

CASE HISTORY

  1. Top of page
  2. Abstract
  3. CASE HISTORY
  4. COMMENTS
  5. REFERENCES

This 50-year-old, right-handed woman began having headaches at the age of 14 years. Her headaches almost always occurred around the time of her menstrual periods or ovulation. This type of hormonal relationship became more consistent by the age of 37 years. She was headache free during her 4 pregnancies. There was also significant improvement of her headaches while she was on birth control pills in between pregnancies. Recently, her periods have become somewhat irregular. Her headache always occurred 1 to 2 days prior to menstrual flow and would continue for a total of 4 to 5 days. There was never any aura. The headache usually occurred in the left periorbital and temporal regions as a sharp pain, which subsequently developed into a throbbing pain. The intensity of the pain increased on physical exertion and bending over. Nausea, photophobia, and phonophobia often accompanied the headache. The headache was rarely disabling. There were no neurological symptoms during the headache. The pain would generally switch to the right side in 2 days, occurring in the same distribution and having all the same clinical features.

The patient is in excellent health with no history of cardiac disease, hypertension, hyperlipidemia, or diabetes. She is a nonsmoker. There is a past history of a benign thyroid nodule.

She had used sumatriptan injection or tablets to treat her headaches ever since they became available. This drug was effective in controlling the headache but caused tightening of the jaw and throat muscles lasting for half an hour, which was very uncomfortable. She used zolmitriptan tablets for the first time in June 1998. They were equally effective but without the uncomfortable side effects of sumatriptan. The patient developed a headache on July 23, 1998, and treated this successfully with zolmitriptan, 2.5 mg. The next day, her headache returned and was again treated with either a 5-mg or a 2.5-mg dose with good control. On the third day, she used another 5-mg dose that controlled the headache again. She was able to function well throughout those 3 days. On the morning of the fourth day, she woke up at approximately 4:00 am with another headache and took either a 2.5-mg or a 5-mg dose of the medication. She went back to sleep and woke up at 7:00 am when she noticed numbness of her right foot. By mid morning, she had developed hypersensitivity to touch and cold all the way up the trunk to just above the umbilicus on the right side. She also noted numbness on the right side of her genitalia with decreased sensation on urination and loss of vaginal sensation. She had some dribbling of urine. Subsequently, she noted inability to achieve orgasm. She also had a problem with decreased rectal sensation. There was no weakness of the lower extremities. There were no symptoms in the left lower extremity or the upper extremities. Initially, there was an area of aching around the thorax on the right side along the upper margin of the sensory loss. Examination revealed normal cranial nerve, motor, and cerebellar functions. Sensory examination revealed absent pain and temperature sensation below T9 level on the right side, including the genital area. There was consistent hyperesthesia over these areas. Touch, joint position, and vibration sensations were normal. There was no tenderness or deformity of the spine.

An MRI scan of the spine was performed on July 27, 1988, which revealed no changes in the cord signal in the cervical or thoracic areas. There were osteophytic changes at C4 through C6 levels with no spinal cord or root compression. Blood counts and chemistry panels were normal. Sedimentation rate, anticardiolipin antibodies, lupus anticoagulant, PTT, PT, and INR were normal. Initial ANA was reported positive at 1:320 with a speckled pattern. A repeat study revealed ANA to be positive at 1:160. An MRI scan was repeated on August 19, 1988, which revealed a focal area of T2 hyperintensity on the left side, involving the anterior part of the cord at T7 (Figures 1 and 2). An MRI scan of the brain was normal except for a few nonspecific bright signals on T2 images.

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Figure 1.–. MRI scan of the thoracic spinal cord showing a lesion with T2 hyperintensity at T7 level on the left side, primarily involving the lateral spinothalamic tract.

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Figure 2.–. A transverse section demonstrating the same lesion.

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Gradually, the patient noted improvement in urination and rectal sensation. Numbness of the vagina and difficulty in achieving orgasm has persisted. She complains of paresthesia in the area of loss of sensation, which is often uncomfortable and interferes with sleep.

COMMENTS

  1. Top of page
  2. Abstract
  3. CASE HISTORY
  4. COMMENTS
  5. REFERENCES

This 50-year-old woman has a typical history of menstrual migraine, which began during her teenage years. She developed neurological symptoms within 3 hours after the use of the last dose of zolmitriptan. Her symptoms progressed rapidly over a short period of time and have persisted since then. The symptoms and signs indicate a lesion involving primarily the left lateral spinothalamic tract at T9 level. The initial scan did not reveal any abnormality, but the repeat scan revealed a lesion on the left side at T7, involving the anterior and lateral aspect of the cord anatomically corresponding to the location of spinothalamic tract. The rapid onset of symptoms and the rapid, but brief, progression followed by stabilization would suggest that this is an ischemic lesion. There has been some improvement of the urinary and rectal symptoms over a period of a few weeks. The development of these symptoms 3 hours after taking zolmitriptan suggests that the drug may be responsible for the infarction. There are no known risk factors for vascular disease, and there is no evidence for any other cause to explain the occurrence of a spinal cord infarction.

There are rare reports of myocardial infarction as a result of using triptans. 1–6 In most of these situations, the patients had risk factors for vascular disease that were overlooked. There are four published reports of stroke associated with the use of sumatriptan. 7–10 In none of these cases could the stroke be unequivocally linked to use of the drug. In one patient, the neurological event occurred several days after the use of sumatriptan. In the second patient, the neurological manifestations were later attributed to the possible development of multiple sclerosis. 7 In another instance, the symptoms of sagittal sinus thrombosis in a 22-year-old woman using birth control pills were misdiagnosed and treated as migraine. This resulted in a cortical infarction. 8 Jayamaha and Street reported the development of a fatal cerebellar infarction in a 39-year-old man with a medical history of severe migraine, elevated serum cholesterol, and a family history of ischemic heart disease. 9 Meschia et al 10 reported the case of a 43-year-old man with no past history of migraine who developed reversible segmental cerebral vasospasm with a left occipitoparietal infarction following the excessive concomitant use of isometheptene mucate and sumatriptan. No other cause was found to explain the vasospasm. To our knowledge, there are no case reports of neurological complications from the use of zolmitriptan. It is comforting to know that the incidence of neurological complications resulting from the use of these highly effective drugs is extremely rare despite the very large number of patients who have received these drugs.

Another possibility to consider is that the neurological event is a complication of migraine itself and not related to the treatment. There are some clinical and epidemiological data suggesting this possibility. However, the information available so far is very limited and inconclusive. 11–14

The patient discussed here provides the first documented case of spinal cord infarction during the use of zolmitriptan and for that matter of any triptan that is available on the market. There were no known risk factors for vascular disease. The close temporal relationship between the use of the medication and the occurrence of the neurological manifestations and the subsequent clinical course support the diagnosis of an ischemic lesion of the spinal cord that may be related to the use of zolmitriptan. The main purpose of this case report is to draw attention to the theoretical possibility of ischemic complications and to urge other clinicians to be on the lookout for similar cases to see whether a cause-and-effect relationship may be established.

REFERENCES

  1. Top of page
  2. Abstract
  3. CASE HISTORY
  4. COMMENTS
  5. REFERENCES
  • 1
    Main ML, Ramaswamy K, Andrews TC. Cardiac arrest and myocardial infarction immediately after sumatriptan injection. Ann Intern Med. 1998;128:874.
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    Jayamaha JEL & Street MK. Fatal cerebellar infarction in a migraine sufferer whilst receiving sumatriptan. Intensive Care Med. 1995;21:82-83.
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    Meschia JF, Malkoff MD, Biller J. Reversible segmental arterial spasm and cerebral infarction. Arch Neurol. 1998;55:712-714.
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    Buring JE, Hebert P, Romero J, et al. Migraine and subsequent risk of stroke in the Physician's Health Study. Arch Neurol. 1995;52:129-134.
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    Tzurio C, Tehindrazanarivelo A, Iglesias S, et al. Case-control study of migraine and risk of ischemic stroke in young women. Br Med J. 1995;310:830-833.
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    Narbone MC, Leggiadro N, La Spina P, et al. Migraine stroke: a possible complication of both migraine with and without aura. Headache: The Journal of Head and Face Pain. 1996;36:481-483.
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    Merikangas KR, Fenton BT, Cheng SH, et al. Association between migraine and stroke in a large-scale epidemiologic study of the United States. Arch Neurol. 1997;54:362-368.