Timothy C. Hain, MD, Chicago IL.• Page last modified: March 6, 2021
|White matter lesions in a patient with well documented complicated migraine (i.e. migraine with stroke).|
MRI scans may reveal white matter lesions in young persons with migraine. These can be and are often are confused with white matter lesions due to multiple sclerosis or white matter lesions that occur in older people (periventricular white matter lesions).
Brownlee (2018) commented in an editorial entitled "misdiagnosis of multiple sclerosis", that as Abraham Maslow commented, "If you have a hammer, everything looks like a nail ?" He discusses the problem that Neurologists often overdiagnose MS by depending on white matter lesions, and being overly generous about attributing symptoms to MS. According to a recent article in Neurology by Solomon et al, the criteria are "only applicable to patients with typical clinical presentations such as MS such as unilateral optic neuritis, brainstem syndromes, and partial transverse myelitis". In other words, white spots by themselves are not enough. In addition, there must be "objective evidence of a lesion". In other words, numbness and tingling with white spots is not enough either. This recent article underlines the problem that many people with migraine (and white spots on their MRI) are wrongly diagnosed as MS. The misdiagnosis of MS is very costly both to patients as well as to society, as current treatment for MS is extremely expensive due to the cost of medication.
In older persons with white matter lesions, migraine is generally not invoked as a potential cause as there are ample other processes to blame. The image above shows a Flair MRI from a patient with well documented complicated migraine (i.e. migraine with stroke). Similar MRI pictures are seen in persons with the more common type of migraine, migraine without aura, and certainly in persons with no migraine at all (where they are usually blamed on "small vessel disease"). This anything goes situation with respect to white matter lesions and migraine probably reflects the underlying lack of homogeneity in migraine -- i.e. "migraine" is really not a "disease", but rather it is a collection of symptoms enumerated by a headache society. Migraine is very inclusive -- and there is room in the symptom list for many distinct diseases.
Bashir et al (2014) separated out three types of structural changes in the brains of persons with migraine-- white matter abnormalities (the subject of this page), infarct-like lesions, and shrinkage. It seems to us that infarct-like lesions could easily include white matter abnormalities. Bashir and associates did not make any strong conclusions, they said that migraine "may be a risk" for structural changes, and that "the clinical and functional significance of these brain lesions is uncertain".
Returning now to migraine patients, between 12-47% of patients with migraine have these white matter lesions, compared to 2-14% of controls (Evans and Olesen, 2003; De Benedittis and Lorenzetti, 1995; Toghae et al, 2015). A recent study has suggested that these are mainly seen in women (Palm-Meinders et al, 2012). This has also been our general experience in our practice, as we note roughly a 4:1 ratio of women to men in our migraine population. We have seen several patients in whom we believe MS was misdiagnosed, based on observation of white matter lesions. As MS is rare, and migraine extremely common (roughly 14% of population), there is a substantial chance of a false positive diagnostic error. More recent studies have not suggested such a dramatic difference between Migraine and everyone else, but there are certainly subgroups within the "migraine" group of disorders that have more white matter lesions than other people of the same age.
In a studies of children with migraine, Mar reported that 6% had similar lesions (10% in migraine with aura, 4% in migraine without aura). These lesions were no more prevalent than normal controls, and were not associated with stroke (Mar et al, 2013). In another study of children and adolescents, white matter lesions were found in 17%, with no relationship between migraine type or presence of a PFO (patent foramen ovale). Bayram et al (2013) found only 4.4% had white matter lesions. All agree that these lesions in children are not progressive or associated with neurological deterioration. Hamedani et al (2013) suggested that they are also not especially progressive in adults, and that they likely occur at younger ages.
While these lesions can appear alarming in persons with migraine, in our experience, generally they are not associated with any neurological disturbance. According to many authors, the clinical significance of these lesions in migraine is unclear (Evans 2003; Dahlof 2005; Bashir et al, 2014). This was also the conclusion of Palm-Meinders et al (2012), who reported that there is no cognitive decline. Possibilities include relationship to migraine, an incidental finding, other medical conditions, or comorbidity of other diseases. As hypertension is associated with more white matter lesions (Sprint group, 2019), and headache is associated with hypertension as well, perhaps these white matter lesions are simply a reflection of uncontrolled blood pressure spikes in persons with severe head pain.
An inherited condition called CADASIL should be suspected in migraine patients with a prolonged typical aura and white matter lesions. Mitochondrial myopathy, antiphospholipid antibodies, SLE, and MS should also be considered in this situation.
The phenomenon of CADASIL points out that Migraine may not be one disease. As Migraine is a "committee diagnosis", it may easily contain within it many distinct diseases, and furthermore, one diseases treatment might not work for another. Recent genetic studies in migraine would support this idea as well. It may be that there is a gene or group of genes, associated with headaches, that is responsible for white matter lesions. In the future, we may want to split up migraine into subvariants, one of which is migraine with white matter lesions. In our practice in Chicago, we often start with verapamil for prevention of migraine with white matter lesions.
According to Sacco and Kurth (2014), "There is currently no direct evidence to support that a migraine prophylactic treatment will reduce future stroke risk in secondary prevention." Or in other words, medications that reduce headache, are not currently shown to reduce white matter lesions, which presumably reflect brain damage. We disagree that the "lack of proof of an effect" is the same as "proof of lack of an effect".
Nevertheless, when abundant white matter lesions are seen, it is the author of this review's policy to encourage the patient to consider use of migraine prophylactic medications, especially those that reduced blood pressure (see below), and avoid vasoconstrictor medications such as "triptans". Our thought is that, in persons with migraine and with a moderate to large number of lesions for age, it is safest to assume that they are caused by migraine, and make a vigorous attempt to treat migraine with prophylactic medications. Medications that we would want to generally avoid in this situation are vasoconstrictors (i.e. triptans, "midrin", "Excedrin Migraine", and the CGRP family of drugs. As venlafaxine can raise blood pressure, we would also be biased against its use. Estrogen supplementation increases coagulability, and we would also be reluctant to use this as migraine treatment in this situation.
In our own opinion, medications that lower blood pressure and migraine both (such as verapamil or beta-blockers), reduce focal neurologic symptoms and probably also reduce the rate of white matter disease. One would expect reduced increase in white matter disease from any medication that lowers blood pressure (Sprint group, 2019).