Cannabis use in patients with multiple sclerosis

Just read a study in Neurology about the effects of marijuana in patients with multiple sclerosis. It seems that MS patients who smoke marijuana have more cognitive dysfunction and mood disorders as compared to MS patients that do not. MS patients may be smoking marijuana recreationally or they may be using it to get rid of tingling and other paraesthesias.

Multiple sclerosis itself causes cognitive problems and if patients smoke marijuana it seems they compound them. With the limited data available to us currently, it is probably wise that patients with multiple sclerosis avoid smoking marijuana.

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

Visit and participitate in my blog:

https://braindiseases.wordpress.com

Visit the brain care foundation website at:

www.braincarefoundation.com

MS treatment related issues

Let us continue to talk about some issues which arise during the treatment of multiple sclerosis.

 

1) How does the disease pan out: Let me try to give you a broad overview of what to expect if you have been diagnosed with multiple sclerosis. I want to stress that this by no way applies to every patient, because each patient’s disease behaves in its own unique way. Initially as I stated earlier, multiple sclerosis has a remitting and relapsing course. You have an attack, it causes some deficits (weakness, numbess, vision loss or gait and balance problems) and then the attack remits and patient may come back to his or her baseline functioning (meaning there are no residual deficits left behind). When multiple sclerosis behaves in this manner it is said to have a relapsing and remitting course (RELAPSING AND REMITTING MULTIPLE SCLEROSIS OR RRMS).

As the disease progresses though and the patient continues to have more attacks, it is seen that the patient does not remit or revert back to the baseline (meaning that some deficits are left behind like some residual weakness or numbness, some problems with balance, tremors etc). When this occurs the patient starts to incur some disability and the disease is said to enter a progressive course (SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS OR SPMS).

As I stated earlier patients in SPMS stage start to get disabled whether it is due to excessive weakness, fatigue or problems with balance or a disabling tremor. As doctors we try to grade their progression in this stage and there are various scales we use. One of the most commonly used scale is the Expanded Disablility Status Score or EDSS. This is a 10 point scale and when a patient reaches midway like around 5 to 6, he or she starts to need assistance with walking and further on may need a wheelchair for ambulation.

The intention behind using the interferons and other immunomodulatory drugs like copolymer (Copaxone) is to prevent or rather delay the progression from a RRMS to a SPMS.

Hence the rationale behind treating all patients aggressively from the onset. Once the patient is in a SPMS state, the medications are continued and different medications might be added to try to halt and delay the disease progression.

 

Till now we do not have any drugs which change the natural history of the disease (meaning cure it!!), all we have are medications which may delay the progression.

 

 There are a certain subgroup of MS patients who have a progressive downhill course right from the onset of the disease (meaning in them the disease does not follow a relapsing and remitting pattern rather they continue to incur more and more neurological deficits). These patients as you can imagine have a poorer outcome and this pattern of disease progression has been referred to PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS OR PPMS

 

Healthy brain and a healthy mind

What do you want to learn about?

I would like to request the readers of my blog or the visitors to my website http://braindiseases.info to tell me what they would like to read or learn more about. I am trying to get more information about MS and ALS out there. I would appreciate if you either drop me an email or write a post about conditions pertaining to you even a very specific question. That would enrich this discussion and make it more worthwhile to all the readers at large.

Please read my new posts about issues pertaining to MS treatment on my website http://braindiseases.info .

Personal Regards,

Nitin Sethi, MD

Issues that come up during MS treatment

Let us now talk about some issues which come up when you are diagnosed with MS.

1) What happens next?

so you are diagnosed with multiple sclerosis what now? Do you need to start  some multiple sclerosis drug immediately? This is a tough question and something which only your doctor can best decide after reviewing all investigations and MRI brain scans. Multiple sclerosis is in its typical form has a relapsing and remitting course. By that I mean, a patient may present with an acute attack of MS like weakness or unsteadiness or loss of vision in an eye (optic neuritis) but then the attack remits and the patient may come back to his or her baseline with at times no residual signs and symptoms. Then there may be a length of time when the patient experiences no fresh attacks. So the question is when do we start treating the disease. Research has shown that even though the patient may have no clinical attack (no overt manifestations of MS), the disease is still relentless and proceeding in the brain. How do we know this? Simple if you repeat the MRI in even an asymptomatic patient, the MRI shall show new lesions (meaning new plaques are seen in the brain MRI suggesting radiological progression of the disease).

Further research has also shown that these lesions (plaques) in the brain add up and contribute to the final disability. The more the number of plaques in the brain (we refer to this as the plaque burden), the more is the final disability and the cognitive difficulties experienced by the patient.

So now the thinking among MS specialists is to treat early and to treat aggressively. The longer you wait, the more is the damage to the myelin and axons (nerve bundles) in the brain. That said and done each patient’s disease behaves in a unique way. There are a small group of patients who have what is called as benign MS. These patients show little or no disease progression over years both clinically and radiologically. Why some patients have this benign form of the disease no one knows but remember it is very difficult if not impossible to know at the onset if a patient is going to have a benign form of MS or not. Hence usually MS specialists would recommend treating right from the onset.

2) Which interferon to use and which is better?

This is another issue which comes up during MS treatment. There are 3 different kinds of interferon available on the market: interferon beta 1b (marketed as Betaseron) and interferon beta 1a (marketed as Avonex and Rebiff).  Without going too much into detail, there is some evidence to suggest that interferon beta 1 b (Betaseron) may be more effective than interferon beta 1a (Avonex).

Betaseron has to be given three times a week (every alternate day) and it has to be injected subcutaneously (under the skin). Avonex on the other hand needs to be given just once a week and it is given intramuscular (inside the muscle and thus more painful shot than a subcutaneous shot). That said and done since Avonex is given once a week it is far more convenient and does not interfere with a patient’s lifestyle as compared to something which needs to be given three times a week.

There is also the issue of neutralizing antibody formation. Simply put it has been seen that if someone takes interferon for a long time, the body starts to form antibodies against it. These antibodies have been referred to as neutralizing antibodies and if a patient has a high titre of these antibodies, it may neutralize the effect of the interferon (meaning make the interferon less effective). Some research has shown the patient’s who take Betaseron develop neutralizing antibodies at a higher rate as compared to those on Avonex or Rebiff. Again your doctor shall guide you through this decision making process.

 

Need more information: email me at neurologistnyc@yahoo.com

 Visit my website: http://braindiseases.info  if you seek further information on some common neurological conditions.

Multiple Sclerosis

Here I shall try to give you a broad overview of Multiple Sclerosis (MS). Multiple sclerosis is a demyelinating disease of the central nervous system (CNS). In the CNS, the axons  are covered by myelin. The axon is the long slender projection of the nerve cell (neuron) that conduct’s nerve impulses away from the body of the cell. The axons in the CNS are coated / covered with myelin, an electrically insulating layer made of phopholipids (a kind of fat). Schwann cells supply the myelin for peripheral neurons ( neurons outside the brain), whereas oligodendrocytes ( a type of cell found in the brain) supply myelin for axons of the CNS.

MS is characterized by demyelination of these axons, that is some process starts to destroy the myelin leading  to loss of myelin. As the disease progresses even axons get destroyed.

Just what sets off this process is still not clear. Various infectious agents and environmental factors have been postulated but none conclusively linked to MS causation.  As a disease MS is more common in Caucasians and more common as you head further from the equator both in the Northern and Southern hemisphere. Thus the incidence of disease is more in Ireland than say in Sub-Saharan Africa. Why you may ask and the answer is no one knows. Maybe it is an environment factor.

Fifteen years of age is the cut off. So if you were born in a country which has a low incidence of MS such as in Asia or Africa and then emigrate to a country with a higher incidence of MS such as Ireland or Canada after the age of 15, you shall carry that low risk of the country of birth with you but if you emigrated say around 6 years then your risks of developing MS go up to the risk of a native in Ireland or Canada.

MS is more common in women as compared to men but when it does occur in men it is usually more severe.

Clinical presenting features of MS-MS has been rightly called the great mimicker in neurology. It can present with a myriad of clinical signs and symptoms which are referrable to both the brain as well as the spinal cord. MS typically presents in the following ways:

1) Isolated attack of optic neuritis: the usual history is a young to middle aged woman who presents with sudden and rapid onset of loss of vision in one eye at times associated with pain on moving the eyes. This occurs due to demyelination of the optic nerve (the nerve which is involved in vision). If the attack remains confined to the optic nerve, this is referred to as a Clinically Isolated Syndrome (CIS). Not all patients with a CIS go on to develop MS, as there are other causes of optic neuritis besides MS.

2) Numbness or weakness in one part of the body.

3) Visual complaints like double vision (diplopia), eyes not moving well (weakness of a muscle of the eye).

4) problems with balance and coordination.

5) ataxia and tremors (patients have a prominent tremor in their hands or in their trunk, as well as are off balance while standing or walking). This is due to involvement of the cerebellum and cerebellar pathways by the MS demyelinating process.

6) problems with bladder control leading to urinary incontinence.

7) Weakness in the legs (paraplegia or paraparesis)–if MS involves the spinal cord, it may cause weakness of both the legs. This condition is referred to transverse myelitis or transverse myelopathy.

So what are the presenting features of MS? MS can present in various fashions, at times the presenting features are vague and this may lead to a delay in diagnosis. The commom presenting features of MS are as follows:

1) MS may present acutely as an attack of optic neuritis. Opitic neuritis is inflammation of the optic nerve and hence the patient seeks medical attention for acute loss of vision and pain in the eye. If this occurs in a young women or man, MS should be borne in mind though there are numerous other causes of loss of vision. Patient may also complain of a desaturation of the color red ie the color red does not appear as bright and ” red” as it used to.

All attacks of optic neuritis do not necessarily lead to MS. Hence this limited presentation at onset is referred to by doctors as a ” clinically isolated syndrome“.

To be certain that your presentation is indeed isolated, your doctor shall have to take a thorough history to make sure you have never had any other attacks suggestive of MS in the past. MRI of the brain and spine as well examination of the cerebro spinal fluid is carried out to rule out any other silent lesions of MS. If no other lesions/ plaques of MS are found in the brain or spinal cord on MRI and the spinal fluid comes back normal then and only then one has a clinically isolated syndrome.

Patients who have a clinically isolated syndrome do not warrant treatment with MS specific drugs like interferons. Your doctor might give you a short course of IV and oral steroids to hasten the recovery of eye function. Most patients who have optic neuritis regain their visual acuity.

2) Numbness or weakness in an arm or leg; patients with MS may present initially with complaints of numbness or weakness in an arm or leg. This usually occurs due to involvement of motor and sensory pathways in the brain or spinal cord by MS lesions.

3) Weakness in legs: if the MS lesions involve the spinal cord, patients may present with more symmetrical involvment like numbness or weaknes in both legs (paraparesis). This condition in which MS lesions are seen in the spinal cord is referred to acute transverse myelitis.

4) Problems with balance and incoordination; MS lesions frequently involve those parts of the brain which control balance and coordination (cerebellum). Thus MS patients frequently have problems with balance and are ataxic ( drunken like gait). They have a prominent tremor in their hands and feet especially when they try to reach out to touch something. These problems with gait and balance are one of the major causes of disability and morbidity in patients with MS.

5) urinary incontinence and sexual dysfunction: MS patients may experience erectile dysfunction and urinary incontinence is very common in female MS patients.

6) Double vision: MS patients may complain of seeing double (diplopia), this occurs due to involvement of tracts in the brain which control eye movements ( an example of such a tract which is frequently involved in MS is medial longitudinal fasiculus or MLF)

Thus as you can imagine MS can present with a myriad of symptoms and the diagnoisis may not be made at the first presentation. It is usually a constellation of signs and symptoms which do not localize to any one particular area in the brain or spinal cord which makes doctors think of MS as the differential diagnosis.

Thus as I stated earlier MS is a disease which is characterized by plaques (MS lesions) which are disseminated in space ( different areas in brain and spinal cord) and time (clinical attacks occur at different times in a person’s lifetime).

 

Diagnosis: how is the diagnosis of MS finally confirmed? Let us discuss that now. As I stated earlier if you present with certain clinical signs and symptoms your doctor may entertain the diagnosis of multiple sclerosis.

Now once the diagnosis is entertained how do you go about confirming the diagnosis. This is usually done with the aid of an MRI of the brain and spinal cord which may show the characteristic plaques of demyelination. Your doctor may also want you to get a spinal tap (lumbar puncture). Lumbar puncture or LP is a test where in a needle is inserted into your lower back to get some of the cerebro-spinal fluid (CSF). About 10-15 ml of CSF is usually removed and sent to the laboratory for various tests. We look for some markers of MS in the CSF. If they are present, they strengthen the case for MS. At times, tests like MRI brain and spinal cord as well as lumbar puncture are unrevealing or non-diagnostic, in that case your doctor may order other tests like visual evoked potential (VEP) and somatosensory evoked potential (SSEP).

Certain diseases like for example Lyme disease, sarcoidosis can mimick MS in their presentation both clinically as well as on the MRI. Hence in appropiate circumstances more tests may be ordered to rule out these conditions.

 

Treatment of Multiple Sclerosis: There are now many treatments available for MS. Here I shall list a few of them without going into too much detail.

Treatment of an acute attack of MS: patients may present to the hospital with an acute attack of MS. This may involve an acute episode of optic neuritis presenting with pain and visual loss in the affected eye or they may present with increased weakness or lethargy. Acute attacks of MS respond well to corticosteroids. Usually steroids are given intravenously at high doses for about 3-5 days. Steriods help in aborting the attack and hasten recovery but they do not change the natural history of the disease (meaning that the MS disease process still continues its relentless progression).

To change the natural history of the disease, drugs that modulate the immune system are used. The most commonly used drugs are :

1) Interferons–usually interferon beta 1 b or interferon beta 1 a. Interferon beta 1 b comes by the brand name of Betaseron while interferon beta 1 a comes by two brand names: Avonex and Rebiff. When compared to each other, the interferons have some difference with respect to potency, easy and frequency of administration. You doctor shall help decide which interferon is best for you. All the interferons have some common side-effects namely injection site reactions, depression, hypothyroidism etc.

2) Glatiramer acetate also called Copolymer 1 -marketed under the brand name Copaxone.

3) Mitoxantrone

4) Natalizumab marketed under the brand name Tysabri