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Keywords:

  • periaqueductal gray matter;
  • migraine;
  • multiple sclerosis

Objective.—To determine if the prevalence of migraine-like headache in patients with multiple sclerosis (MS) is associated with plaques in the brainstem or in other locations.

Background.—There is increasing evidence to suggest that periaqueductal gray matter (PAG) plays a role in the pathophysiology of migraine headache. There are a few clinical case studies and some experimental evidence in support of this observation.

Methods.—The study population of patients with demyelinating disease was identified by accessing the Department of Radiology magnetic resonance imaging (MRI) database accumulated between the years of December 1992 and June 2002. A total of 4369 MRI scan reports were available for review from that time period. Out of this, 1533 studies were reported to have possible demyelinating lesions. Medical records of these patients were reviewed to confirm the diagnosis of MS and also to document the headache complaints, if any. Two hundred and seventy-seven patients were identified with definite MS. A questionnaire was mailed to these patients to obtain additional details regarding MS and headache. The questionnaire response rate was 61% (169 of 277). This data were added to the information previously obtained from the medical records. The MRI films of each patient were examined, documenting location of the plaque, rather than the actual number. MRI and clinical data were kept separate until the final analysis. The International Headache Society criteria were used to classify headache types.

Results.—There were 207 female and 70 male patients available for analysis. Sixty-six percent (182 of 277) of patients were diagnosed with remitting-relapsing MS, 17% (47 of 277) with primary progressive MS, and 17% (48 of 277) with secondary progressive MS. Overall, 55.6% (154 of 277) of patients had a complaint of headache. Of these patients, 61.7% (95 of 154) met criteria for migraine-like headache, 25.3% (39 of 154) met criteria for tension-type headache, and 13% (20 of 154) had features of migraine and tension-type headache. MS patients with a plaque within the midbrain/periaqueductal gray matter areas had a four-fold increase in migraine-like headaches (odds ratio 3.91, 95% confidence interval 2.01 to 7.32; P < .0001), a 2.5-fold increase in tension-type headaches (odds ratio 2.58, 95% confidence interval 1.13 to 5.85; P= .02), and a 2.7-fold increase in combination of migraine and tension-type headaches (odds ratio 2.77, 95% confidence interval 0.98 to 7.82; P= .05) when compared to MS patients without a midbrain/periaqueductal gray matter lesion. Although not statistically significant, MS patients with three or more lesion locations were found to be approximately two times more likely to have migraine-like headaches compared to MS patients with 0 to 2 locations (3 to 5: odds ratio 2.47, 95% confidence interval 0.90 to 6.84; 6 to 8 locations: 1.82, 0.64 to 5.17; ≥9 locations: 2.41, 0.63 to 9.13). A linear trend was also observed between numbers of lesion locations and migraine-like headaches (P= .02).

Conclusion.—The results of this study indicate that the presence of a midbrain plaque in patients with MS is associated with an increased likelihood of headache with migraine characteristics.