White matter disease of the brain: what do we know about it? Should I worry?

I frequently get asked about white matter disease of the brain. It is commonly reported when MRI scans are carried out causing concern to patients and family alike. So in this blog post that is the topic we shall discuss.

Just what is white matter disease of the brain? As you all may be aware of in very simple terms the brain is made of grey matter (comprising the cell bodies of the neurons) and white matter (fiber tracts). Think of white matter disease as changes seen in the white matter of different parts (lobes) of the brain visualized on a MRI scan of the brain. Either the white matter appears scarred or atrophic. If the white matter is examined under the microscope, degenerative (ischemic) changes are visualized in the small blood vessels hence the term ischemic microvascular small vessel disease is sometimes used. A point to remember here is that these white matter changes visualized on the brain MRI can be seen in many different diseases of the brain-diseases as diverse as leukodystrophies, nutritional deficiencies, toxic drug exposures, vascular dementia and multiple sclerosis (MS). So the radiologist’s report invariably lists all these differential diagnoses and when patients read their MRI report they get worried. Many write in to me asking me if they have MS.

White matter changes on brain MRI need to be correlated with the patient’s history and examination findings and that is where I as a neurologist step into the picture. Let me explain with a few examples:

1. A 29-year-old woman with history of acute loss of vision in one eye (optic neuritis) . MRI brain shows white matter lesions in a characteristic distribution (perpendicular to the long axis of the lateral ventricles). In this case multiple sclerosis is high up in the differential.

2. A 29-year-old woman with history of episodic headaches which are usually unilateral, throbbing in quality and accompanied by nausea and photophobia (brights lights bother her during the headache episode). MRI brain shows a few non-specific white matter lesions scattered in the brain. In this case the most likely diagnosis is migraine headaches.

3. A 75-year-old woman with complaints of memory impairment. MRI brain shows white matter lesions scattered diffusely in the frontal and temporal lobes. In this case vascular dementia is the diagnosis which comes to mind.

Should white matter disease of the brain be treated: if the white matter disease of the brain represents ischemic white matter disease it may be prudent to address vascular risk factors such as better control of hypertension and diabetes, lowering the cholesterol and advising the patient to stop smoking. There is now increasing evidence that white matter disease may cause cognitive impairment and may coexist with other causes of memory impairment such as Alzheimer’s disease in the same patient. On the other hand if the white matter lesions are demyelinating lesions of MS, then treatment is aggressive treatment of MS. If they are due to migraine then usually no treatment is warranted.

In children the cause of white matter disease of the brain is different. Various leukoencephalopathies, metabolic, hereditary and degenerative diseases are in the differential and have to be screened for and ruled out systematically.

I hope this small post helps to answer some of my readers concerns.

Nitin K Sethi, MD

White matter lesions, migraine and memory problems: a question and an answer

One of the readers of my blog wrote in with a question about white matter lesions on brain MRI. Her question and my response to it follows.


I was recently referred to a neurologist by my primary care physician for treatment of my migraines. While migraines have a been a part of my life, they have been occuring with greater frequency of late (10+ per month). To rule out any other cause of my migraines, the doctor ordered an MRI. The MRI revealed 20+ white matter lesions throughout my brain (various locations, various sizes). The neuro was at a loss as to why I had so many. I did inform him that approx 15 years ago I had unilateral ect, and asked if perhaps this had caused it? I also let him know that I was experiencing significant memory issues (forgetting short term and long term memories, and even blanking on spelling my own last name for a minute or two). I asked him if ect could be responsible? The neuro has since followed up with me and has stated that ect could NOT be responsible for the lesions, and was not likely to be responsible for my recent, memory issues. I have been tested for MS, lyme, infection, etc. – all negative. I do not suffer from depression or take any other medications which would cause memory issues. Any thoughts? What else could cause these lesions? Is these any research at all into lesions and ect? I am trying to get into Neuropsych testing to determine the extent of my memory loss. The migraines are now currently being sufficiently controlled with Imitrex.


Thank you for writing in to me M.  White matter lesions are commonly documented on brain MRI done for various reasons (in your case as a work up of migraines). The differential diagnosis of white matter lesions is broad and varies based on the age of the patient. In “most” adult patients especially those with risk factors for microvascular disease such as diabetes mellitus, essential hypertension (high blood pressure), dyslipidemia (high cholesterol), current or past heavy smokers these white matter lesions respresent small vessel disease (also referred to as microvascular ischemic small vessel disease). Meaning that the small blood vessels in the brain are showing signs of ischemia (lack of blood flow). So when I see extensive microvascular (small vessel) disease on a patient’s MRI scan of the brain what I worry about is the possibility of a stroke in the future. As a neurologist, I then try to identify his stroke risk factors and attempt to modify them. If he has high blood pressure and is not an on anti-hypertensive medication–start an appropriate anti-hypertensive, if he is already taking a blood pressure medication but the blood pressure is still not well controlled then I may need to increase the dose of his medication and/or change it. As per the new Joint National Commission guidelines broadly speaking the lower the blood pressure the better it is (earlier a blood pressure of 140/80 mm Hg was accepted as ” normal”, now we aim for level of 120/70 mm Hg). If the patient’s blood sugar is high (fasting blood sugar greater than 107mg/dl), I would investigate him for diabetes mellitus. For this blood sugar is tested in a fasting state and after meal (post prandial). There are normal values and if the patient’s blood sugar exceeds these normal values, then he has diabetes mellitus. Diabetes mellitus can be controlled by a combination of dietary modification, exercise, oral hypoglycemic medications (pills) and/or insulin injections. If the lipid profile is deranged (high total cholesterol, high low density lipoprotein, high triglycerides and low high density lipoprotein), then again dietary modifications, exercise and lipid lowering medications (statin group of medications such as Lipitor are one example) are recommended.

Now what do white matter lesions represent when they are seen in a young person (like for example in a  young lady 25 years of age)?  The main differential and what concerns most patients and physicians alike is whether this could represent multiple sclerosis. I have written about this before and again want to emphasize that the diagnosis of multiple sclerosis is a clinical one and not based solely on the MRI scan of the brain. The MRI scan always has to be interpreted after taking the history and examination findings into consideration. Also the white matter lesions of ischemic small vessel disease are different from the white matter lesions (plaques) of multiple sclerosis. In multiple sclerosis the lesions have a characteristic appearance and distribution in the brain.

White matter lesions can also be seen in many other infectious (Lyme disease is a good example) and inflammatory conditions (sarcoidosis, connective tissue diseases which cause vasculitis in the brain). Most of these diseases can be identified with the help of a good history and some basic tests.

White matter lesions are also commonly seen in people who suffer from migraines (more commonly seen in women migraine sufferers). Why do white matter lesions occur in migraine patients. While there are many theories of migraine pathophysiology, migraine is a vascular headache and hence the blood vessels are again involved.

Do white matter lesions cause memory problems. Now that is a tough question to answer. When I see extensive white matter disease in a brain MRI, it tells me about the health of the brain and the blood vessels. If a person has extensive white matter disease, the same pathology shall be seen in the blood vessels of the heart. So they are prone to both heart disease and brain disease (stroke, transient ischemic attacks). While Alzhemier’s disease is the most common primary dementia, vascular dementia is exceedingly common too. What is vascular dementia? As the name suggests, it is dementia (memory impairment, problems in multiple cognitive domains) caused due to multiple small strokes in the brain or rather strokes in a strategic location. These strokes occur over a period of time and may be clinically silent (meaning that the patient may not even realise that he has suffered a stroke). The small strokes over a period of time though add up and cause vascular dementia.

I hope this helps in answering some of your questions M. My advise to you is to follow up with your primary care physician and the neurologist. They shall help guide your work-up further.

Personal Regards,

Nitin Sethi, MD

White matter lesions in the brain: a question and an answer

One of the readers of my blog asked a very interesting question. I am reproducing her question here. My response to it follows. I hope you shall find it helpful.

Personal Regards,

Nitin Sethi, MD

I am 45 now when I was 25 I was diagnosed as have a pituitary adenoma that caused no active symptoms. Over the years my PCP would follow up with MRI’s and visual field tests. An MRI performed in 03 showed some non specific periventricular high signal white matter changes on the left. Recently in Oct 2010 another MRI was repeated for follow up purposes only. This time it showed several tiny areas of subcortical white matter high signal changes are identified in the right parietal region as well. Pituitary was normal. I am 125 lbs, caucasian femal and I have no neurological symptoms, high blood pressure or diabetes an occasional headache that I get is so mild and I usually pass if off for being tired. My question is what can I do (if anything) to stop these changes from occurring. Does calcium have an effect on this, alcohol consumption (8 to 10 per week) or can cognitive games, etc? Thank you for any input. Best Regards D

braindiseases Dear D,
thank you for writing in. You ask a very good question. Like I explained in my post not all white matter lesions represent MS plaques. The majority of these white matter lesions are what we refer to as ischemic small vessel disease. As the name suggests the pathology lies in the small vessels in the brain. Ischemic white matter disease is more commonly seen as we age. Also patients who have vascular risk factors are more likely to show white matter disease. The common modifiable risk factors are: essential hypertension, diabetes mellitus, dyslipidemia (increased total cholesterol, increased low density lipoprotein and triglycerides and decreased high density lipoprotein), smoking, excessive alcohol intake, obesity and sedentary lifestyle. Some people are hypercoagulable and thus are more prone to strokes and heart disease. Patients who suffer from chronic migraines (especially women) also frequently have “excessive” white matter disease.
Now the million dollar question is whether this white matter disease is harmful to the brain. Does it affect the patient cognitively? There are indeed studies that show that excessive white matter disease may make the person prone to cognitive problems later on in life. This is called vascular dementia. My advise to you would be this:
If you have any of the above vascular risk factors, I would attempt to modify them. Good control of blood pressure is paramount. Earlier a blood pressure of 130/80 or 140/80 was considered acceptable. Nowdays the teaching is “lower the better”. Hence the new guidelines recommend lowering the blood pressure down to 120/70 mm Hg. In the same vein the guidelines with respect to acceptable cholesterol, triglycerides (TG) and low density lipoprotein (LDL) have become more stringent and again the teaching nowdays is “the lower the better”. If you smoke, quit completely as no amount of smoking is good for your heart or the brain. I would advise you to eat a healthy diet rich in vegetables, fruits and nuts. Exercise on a regular basis (cardiovascular exercise such as jogging or brisk walking has been found to be the most beneficial). I usually recommend my patients to take 1-2 tablets of a good multivitamin per day (one that has all the B group of vitamins). Studies have shown that vitamin B12 plays an important role in cognition and so I usually recommend it to most of my elderly patients especially those who are vegetarians and have a marginal diet. I find my patients frequently deficient in Vitamin D (vitamin D is made in the skin from sunlight and so caucasians living in the temperate areas are frequently vitamin D deficient) and so I supplement it. The amount of vitamin D needed on a daily basis varies according to your sex and age and you should consult your primary care physician to determine how much you should take. I usually give my patients around 400 international units of vitamin D per day.
I am a big believer in cognitive games (the fancy word for this now is Neurobics). You can read more about these in my neurobic post here or on my website http://braindiseases.info.
I hope I have addressed your concerns adequately.

Personal Regards,
Nitin Sethi, MD

White matter lesions on MRI–a question and some answers

I thank one of my readers Sandy for writing in.  Sandy asks some important questions. As a lot of you may be dealing with some of the same issues as her, I am reproducing her question here. My answers to her query follow.

Again thank you Sandy for writing in.


Dear Dr.

In june I experienced some very unusual headaches that felt think electrical shocks throughout my head. One night I experienced the worst headache of my life in my forehead only. It lasted all night and in the morning it was better; however I experienced dizziness and if I bent over a swell of pain would radiate through my head. A week later I experienced an eye problem and was told that it was uveitis. Because uveitis can be caused by a virus or autoimmune problem, I immediately began testing for an autoimmune problem. During this testing I continued to experiece overall nerve pain in by head (forehead, temple, back of head) as well as neck pain, should nerve pain through fingers, neck, ankels), joint & chest pain. The only positive test result showed a high ANA test of 1:640 but all other blood tests(c-reactive protein, RF, Sed Rad, SM etc..) were normal. I also had an MRI and the radiologist noted several tiny foci white matter in the frontal lobe area. He indicated that it is may or may not be of clinical significane but could be small vessel ischemia disease or possible dymlienation. I wonder if there is a correlation to the several headache I had in my forehead with the MRI results. My neurologist initially said I had occpital headaches and is normally caused by a pinched nerve; but after receiving this MRI, I don’t think he has it right. I feel the headaches and vision problems along with the other symtoms correlate together. Should I be concerned about this MRI. I don’t feel that this is MS because I’m not having muscular/walking issues; but greatly concerned that if these headaches continue, cognitive problems could occur. Your opinion would be greatly appreciated.

From MRI white matter lesions: does it represent MS?, 2008/09/26 at 2:24 PM


Dear Sandy,

                      thank you for writing in. Your case history is intriguing, since I do not have all the details my assessment is severly limited.  I can though tell you that white matter lesions are commonly seen when patients undergo a MRI study of the brain. Some of the times these white matter lesions (also referred to as white matter hyperintensities (WMH), this is because they appear as bright white spots on the MRI) are incidental findings and may have nothing to do with the reason the MRI was done in the first place. Let me explain. Lets assume you come to see me since you have being lately experiencing headaches. I order an MRI because I want to rule out a brain tumor. MRI result comes back. There is no brain tumor but incidentally note is made of several scattered white matter hyperintense lesions. Likely in the case I describe above, the WMHs are incidental findings and not the cause of the patient’s severe headaches.

So what do these white matter lesions represent? Many diseases can cause white matter lesions in the brain MRI.  One of the diseases usually mentioned in MRI reports is multiple sclerosis. Patients rightly get scared that they may have MS. While multiple sclerosis is characterized by white matter lesions (we call them plaques in the case of MS) which are scattered in the brain, I want to re-emphasize that not all white matter lesions represent MS (see my website for more details http://braindiseases.info). In the case of MS, the plaques are scattered in the brain in a particular way. Moreover if you do not have any signs or symptoms of MS (your examination is normal), more than likely the white matter lesions do not represent MS. The diagnosis of MS is clinical, at times supplemented by tests like MRI brain, CSF/ spinal fluid examination and evoked potentials.

A lot of work has been done to determine the significance of white matter lesions. The thinking now is that they represent ischemia (lack of blood flow) in the small blood vessels of the brain. Hence they are also at times referred to as ischemic small vessel disease. Hence these lesions are more commonly seen in the MRI of patients who have cerebrovascular risk factors like hypertension, diabetes and high cholesterol as well those that smoke. Their incidence increases as we age (meaning you are more likely to see them on the MRI of someone who is 60 and above rather than someone who is in his 20’s).

They have been reported in the MRI of patients who suffer for migraine. The reason they are more commonly seen in migraine patients is again not fully elucidated but the thinking is that migraine is due to vascular causes and hence WMHs are more common in these patients.

While I cannot comment of your case in particular, you have a positive ANA though rest of the autoimmune markers are negative and your ESR is low. I would rule out the usual suspects, vasculitis though remains in the differential and it would be reasonable to make sure you do not have any underlying vasculitic etiology.

Your last question is important. Though there is no direct correlation between the extent of WMHs in the brain and the development of cognitive decline, as I stated earlier they become more common as we age. People who have extensive white matter disease in their MRI frequently do exhibit cognitive deficts when carefully tested for. Whether this represents a form of vascular dementia is not clear.

I would advise you to follow with your PMD and neurologist. They would be the best people to guide further diagnostic workup and treatment.

Personal Regards,

Nitin Sethi, MD

MRI white matter abnormalities

This is to Nancy

Dear Nancy, thank you for your comment to the post on white matter abnormalities on MRI does it represent MS? While it is hard for me to comment on your case specifically, the MRI report reads suspicious for MS. The reason is the lesions are periventricular (around the ventricles of the brain) and such lesions are at times more specific for MS.

I would though correlate this information with your age, your symptoms and importantly your history and clinical examination findings. If there is suspicion for MS from your history or clinical findings, then I would recommend doing further tests to either rule in or rule out the diagnosis of MS. Tests like spinal fluid examination, visual evoked potential and somatosensory evoked potential. As I stated earlier one can see these white matter lesions in patients who have vascular risk factors like hypertension and diabetes mellitus. I am not sure whether the drug you mentioned for RA has been implicated in causing them. You should follow up with your doctor, who would guide you in how to interpret these MRI findings.

Please refer to the MS articles on my website http://braindiseases.info for further information. Feel free to drop me an email if you have any further questions. I wish you my very best.

Personal Regards,

Nitin Sethi, MD

MRI white matter lesions: does it represent MS?

MRI white matter lesions

Many times I get consulted by patients or their relatives when their MRI brain report reads multiple scattered white matter lesions seen. The radiologist’s report usually further reads that these can be seen in primary demyelinating conditions like multiple sclerosis or in vascular disorders. Patient’s and caregivers are naturally worried when they get this MRI report and do not know what to do and how to proceed further. So I thought that here I shall talk about these white matter abnormalities seen on the MRI. What is their significance? Do they represent evidence of multiple sclerosis?

White matter signal changes on the MRI essentially means that on the MRI, the white matter  showed some scattered bright spots. White matter in the brain refers to the fiber tracts that carry information to and fro from the brain.

My first question when somebody asks me what next and what does this mean is to ask them why was the MRI done in the first place. If the MRI was done because there was a clinical suspicion of multiple sclerosis then these white matter lesions may indeed have significance and may represent radiological evidence of MS plaques. Let me explain this with an example. You go to your doctor, you have signs and symptoms that suggest MS (example you may have had an attack of optic neuritis), when the doctor examines you he is able to elict signs in the examination compatible with a diagnosis of MS, then he orders an MRI to see if you do have evidence of white matter lesions in the brain. In a case like this the presence of white matter lesions/ signal changes in the MRI is obviously important. Here it likely does suggest the presence of MS. That said and done I again want to re-emphasize that the diagnosis of MS is made on the basis of clinical history of previous attacks, CSF (spinal fluid) examination and MRI, not just on the basis of the MRI alone. Also there are certain criteria which have to be satisfied on MRI to make a definite diagnosis of MS. These radiological criteria for MS include the number of lesions on  the MRI, their location and their size.

Thus it is important to remember that a person who is noted to have white matter lesions on a brain MRI does not necessarily have MS. White matter lesions can be seen in numerous other conditions and they are more commonly seen as we grow older. The thinking behind this is that they represent microvascular ischemic changes in the brain (the smaller caliber blood vessels in the brain showing signs of ischemia or decreased blood flow). Hence these white matter abnormalities on MRI are more commonly seen in patients who have microvascular and macrovascular risk factors such as a history of hypertension, diabetes and high cholesterol (dyslipidemia/ bad lipid profile).

White matter signal changes on MRI may also be seen in patients who have infectious and other inflammatory conditions. They have been reported in the MRI of patients with a history of migraine headaches (migraine too is a vascular disorder and that may explain the connection).

So I want to end by saying that the presence of these white matter signal changes on brain MRI has to be correlated to the history, clinical examination and other ancillary investigations. Your doctor shall help you in going about this in a methodical manner. I repeat these white matter lesions do not suggest MS in each and every case they are found.

 Dr. Sethi

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