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Neuro- headaches

Primary Care Corner with Geoffrey Modest MD: Migraine and Heart Disease in Women

1 Jul, 16 | by EBM

By Dr. Geoffrey Modest

Analysis of the Nurses’ Health Study found a significant increase in cardiovascular disease in those with migraine

(see ).


  • 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease were followed from the prospective Nurses’ Health Study II (from 1989-2011)
  • Mean age 35; BMI <25 in 68%, 25-30 in 19%; history hypertension 6%, hypercholesterolemia 12%, smoking 14%; no alcohol in 38%, up to 15 g/d in 58%; oral contraceptives in 12%.
  • 17 531 (15.2%) women reported a physician’s diagnosis of migraine (though no data on presence of aura, migraine frequency, or migraine meds)
  • Women with migraine were more likely to have hypertension, hypercholesterolemia, family history of MI, BMI>30 or be current smoker


  • 1329 major cardiovascular disease events occurred, and 223 women died from cardiovascular disease
  • Adjusting for potential confounding factors (age, cholesterol, diabetes, hypertension, BMI, smoking, alcohol, physical activity, postmenopausal estrogens, menopausal status, oral contraceptives, aspirin/acetaminophen/NSAID use, and family history MI), migraine was associated with an increased risk for:
    • Major cardiovascular disease (hazard ratio1.50, 95% confidence interval 1.33 to 1.69)
    • Myocardial infarction (HR 1.39, 1.18 to 1.64)
    • Stroke (HR 1.62, 1.37 to 1.92)
    • Angina/coronary revascularization procedures (HR 1.73, 1.29 to 2.32)
    • Cardiovascular disease mortality (HR 1.37, 1.02 to 1.83)
    • Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current)


  • Several studies have found that migraine (specifically migraine with aura) is associated with increased risk of stroke
  • The Women’s Health Initiative found similar increase in cardiovascular disease (about the same +/- 50% increase as above), but only in those reporting migraine with aura
  • Several other studies from different countries (Taiwan, Iceland, as well as the American Migraine Prevalence and Prevention Study) have found similar results
  • How to explain the association?? Unclear. ?increased thrombogenic susceptibility, shared genetic markers, endothelial dysfunction, or inflammation (all have been shown in both migraine and cardiovascular disease). And a recent small study found that the combination of a statin and vitamin D, perhaps through their anti-inflammatory or endothelial effects, decreased the frequency of migraines (for analysis of this study, see prior blog:
  • So, it probably makes sense to include migraine (perhaps more so if aura present) in the overall gestalt of cardiovascular risk factors – e., it would be an added reason to strongly encourage lifestyle changes (smoking, appropriate weight, increasing fruits/veges in diet, exercise) in general, and it might sway me to use statins in those otherwise on the borderline for medical therapy


Primary Care Corner with Geoffrey Modest MD: Migraine Prophylaxis with Simvastatin/Vitamin D

6 Jan, 16 | by EBM

By Dr. Geoffrey Modest

A small research study found that using the combo of simvastatin 20mg plus vitamin D3 1000 IU bid led to decreased migraine recurrences (see Ann Neurol 2015;78:970​). The basis for this study was that the usual treatments (anticonvulsants, b-blockers, tricyclics) often have problematic adverse effects, and that migraines may involve a component of endothelial dysfunction/vascular inflammation which may improve with a statin and vitamin D.


  • 57 patients with migraine diagnosis and at least 4 migraine-days/month were randomized (mean age 40 in active treatment/28 in placebo!!; 90% women; 4% current smoker; 40% with seasonal allergies; 40% anxiety/depression; 50% on oral contraceptives; 50% on current migraine prevention meds).  Most had migraines >10 years and had tried median of 3 abortive agents in the past. Note that in this small study, many of these %’s differed from the active med vs placebo groups (e.g., number of migraine days was 25.5 in the past 3 months in the active med group but only 18 in the placebo group). Those on migraine prophylactic agents continued taking them. Followed 24 weeks
  • Primary outcome: change in number of days with migraine; secondary outcome: changes in use of acute migraine meds, and migraine disability/duration/intensity/associated symptoms


  • ​Primary outcome: those on active treatment in the first 12 weeks had a decrease of 8 migraine-days (-15.0 to -2.0) vs +1.0 in the placebo group (-1.0 to +6.0), with p<0.001. During the second 12 weeks, there were similar improvements: -9.0 days with active treatment (-13 to -5) vs +3.0 with placebo (+1.0 to +5.0) with p<0.001. And, 29% of those on active meds had >50% reduction in migraine-days vs 3% on placebo
  • Secondary outcomes: those on active meds: used fewer abortive migraine meds, and had both fewer days of meds (p<0.001)and fewer doses of meds (p<0.001); less migraine disability (p<0.001); but no difference in symptoms when migraines did occur, nor of migraine severity/duration/symptoms
  • There were similar reductions in migraine in those continuing with their other prophylactic meds or not
  • ​Regression analysis showed no difference in response by baseline values, including age and BMI, or if baseline < vs >8 migraine-days/month
  • Adverse events: very few, nonsignficant differences (though interesting that there were more myalgias in the placebo group as well as joint/skeletal pain)

So, a few points:

  • The magnitude of this treatment effect (30% fewer migraine-days) exceeds that of many of the other drugs currently used clinically (though actually hard to compare the studies since different study designs)
  • The simvastatin/vitamin D was really well-tolerated, vs the reported 25-50% range discontinuance rates reported for amitryptaline, topiramate, and propranolol.
  • Clearly this was a small and preliminary study. But the results were pretty impressive, for meds that are used all the time​ for other indications, are well-tolerated, and may even have other benefits (vitamin D and bone/?immunologic function; statins and atherosclerosis prevention). Though a bigger study is necessary to confirm the above, I think it is reasonable to try simvastatin/vitamin D in patients with frequent migraine with either minimal response or too many adverse effects of the standard prophylactic meds (and I wonder if combos of this with other meds might be even more effective, since they likely have different mechanisms of action).

Primary Care Corner with Geoffrey Modest MD: Trends in headache diagnosis and treatment

3 Feb, 15 | by EBM

By: Dr. Geoffrey Modest

A rather disturbing article was published on trends in the ambulatory management of headache (see DOI: 10.1007/s11606-014-3107-3). This analysis looked at a nationally representative sample from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (not including ER visits) and excluded those patients with red flags (neurologic deficit, cancer, trauma), with the following findings:

–9362 visits for headache assessed, which represents 144 million visits over the study period of 1999-2011
–mean age 47, 75% female, 75% white
–use of CT/MRI rose from 6.7% of visits in 1999-2000 to 13.9% in 2009-10. The report did not differentiate CT vs MRI.
–referrals to other physicians rose from 6.9% to 13.2%
–but, clinician counseling declined from 23.5% to 18.5% (counseling includes: lifestyle modification, diet/exercise counseling, stress management, discussing potential psychosocial influences on headache)
–use of preventive medications increased from 8.5% to 15.9%
–use of opioids/barbiturates remained unchanged at 18% (which is higher than use of NSAIDs/acetaminophen, which was steady at about 16%, though triptans/ergots rose from 9.8 to 15.4%)
–trends not different if adjust for migraine vs nonmigraine headache, or acute vs chronic presentation
–primary care physicians (PCPs) had lower odds of ordering CT/MRI, though there was a parallel increase over time

In this context, Choosing Wisely published 5 suggestions in 2013, after this study period but highlighting previously circulated guidelines (see here), of which 2 were:

​–Don’t perform neuroimaging studies in patients with stable headaches that meet criteria for migraine. Numerous evidence-based guidelines agree that the risk of intracranial disease is not elevated in migraine. However, not all severe headaches are migraine. To avoid missing patients with more serious headaches, a migraine diagnosis should be made after a careful clinical history and an examination that documents the absence of any neurologic findings such as papilledema. Diagnostic criteria for migraine are contained in the International Classification of Headache Disorders.​
–​Don’t prescribe opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders. These medications impair alertness and may produce dependence or addiction syndromes, an undesirable risk for the young, otherwise healthy people most likely to have recurrent headaches. They increase the risk that episodic headache disorders such as migraine will become chronic, and may produce heightened sensitivity to pain. Use may be appropriate when other treatments fail or are contraindicated. Such patients should be monitored for the development of chronic headache.

So, rather striking doubling of use of imaging studies (and, a recent report found that 62% of head CTs were inappropriate, according to guidelines) and referrals. It is good that more preventive meds are being used, though a little disturbing that so many opiates/barbiturates are still being prescribed. And, rather sad that clinician counseling decreased, as we continue to learn of the common psychosocial associations with headaches, though PCPs did somewhat better at that than non-PCPs. It is likely that part of the reason for decreased counseling is the increasing demands on PCP time (more to do/clinical items to address in a visit, more paperwork, more time pressure overall, and counseling takes more time than ordering a CT/MRI…). So, as an unabashed advocate of primary care, with its attendant deep patient relationships yet continual intellectual stimulation, I do need to rant a bit. This change in headache treatment is yet another example of the failure of our health care system: by its not placing primary care at the center of the system, with appropriate reimbursement to allow the PCPs to have time to address patients’ concerns adequately, the system not only misses an opportunity to decrease costs but also to significantly improve the quality of care.

Primary Care Corner with Geoffrey Modest MD: Choosing wisely re headache…

25 Nov, 13 | by EBM

here is the latest of the choosing wisely suggestions (these are 5 suggestions by different specialties, with an eye to decrease unnecessary testing).  see URL

1.Don’t perform neuroimaging studies in patients with stable headaches that meet criteria for migraine. (no increase in intracranial disease in pts with migraine)

2.Don’t perform computed tomography (CT) imaging for headache when magnetic resonance imaging (MRI) is available, except in emergency settings (MRI more sens in picking up neoplasms, vasc dz, posterior fossa and cervicomedullary lesions, and high or low intracranial pressure disorders. and less radiation to boot…

3.Don’t recommend surgical deactivation of migraine trigger points outside of a clinical trial.

4.Don’t prescribe opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders. they suggest that these meds increase likelihood that the headache disorder will become chronic, increase sensitivity to pain.

5.Don’t recommend prolonged or frequent use of over-the-counter (OTC) pain medications for headache. issue is causing medication overuse headaches


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