My Interview with Doctor Nitin Sethi, Neurologist

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I have had the good fortune recently to get in touch with an amazing blogger who just happens to be a neurologist.   Doctor Nitin Sethi is a neurologist and Assistant Professor of Neurology at New York Presbyterian Hospital and Weill Cornell Medical Center. Doctor Sethi's personal philosophy is to give back as much as he can to the community at large, and he does so with great compassion.   He has agreed to not only grant me the opportunity for multiple interviews, but is also willing to answer reader questions.   I will tell you the details about how you can pose questions to Doctor Sethi in a subsequent post.

I am most honored to introduce to you...

Nitin K. Sethi, Mssistant Professor of Neurology
New York-Presbyteriaospital
Weill Cornell Medical Centeew York
**, NY 1006   Doctor Sethi has written numerous articles** in the field of neurology and you can find many of them here.

He also has a website called   Brain Diseases Information    

(Doctor Sethi's goal is to present medical information to the general population who may not have access to medical and scientific journals.)

You may visit Doctor Sethi at his blog called  Brain Diseases  

(Doctor Sethi writes on numerous topics including Multiple Sclerosis and epilepsy.)

Prior to my official diagnosis of Multiple Sclerosis my doctor ordered some other tests, most notably blood tests to rule out other disorders.   What are some of the other disorders and diseases which can mimic the symptoms of MS?

Multiple sclerosis has been called the great mimicker and there is a reason to this. The initial signs and symptoms of MS can mimic those of many other more common diseases. As I see it there are two kinds of patients. One who, when they present to a doctor, have signs and symptoms so characteristic of MS, that the diagnosis is readily apparent. These are usually patients who give history of multiple attacks suggestive of MS over a period of time. To make a diagnosis of multiple sclerosis one should have at least two attacks which are separated in time and space.

Let me explain this further. Let's assume you go to your doctor because you have been having numbness in your right arm. Your doctor examines you and finds that apart from sensory loss in the right arm, you have other examination findings such as you have ataxia (your gait is off and unsteady), your movements are uncoordinated and you have a   tremor in your  right arm, your eyes do not move well and you have what we call internuclear opthalmoplegia. What I am trying to say is that your examination findings are suggestive of not one but multiple sites of pathology in your brain.

Numbness in the right arm localizes to the sensory cortex on the left side of your brain.

Ataxia might be due to a midline cerebellar problem.

Right  arm tremor localizes to the right cerebellum (cerebellar  pathways are double crossed in the brain).

The eye findings and internuclear opthalmoplegia localizes to the midbrain.

So you have signs that whatever your disease is it is disseminated in space (SPACE AS IN DISSEMINATED IN DIFFERENT PARTS OF THE BRAIN).** Your findings cannot be explained by one single lesion but rather by multiple small lesions.** So you have met the** first criteria** to make a definitive diagnosis of MS-dissemination in space. (OF COURSE DISSEMINATION IN SPACE SHALL ALSO BE CLEARLY SHOWN IF YOU DO A MRI SCAN)

Now how do we prove you have dissemination in time?  Well that is done by history. Lets assume your doctor now asks you" Miss Smith have you ever had a problem with your eye before? Did you ever lose vision in one eye?"

Miss Smith: "Now that you ask doctor Sethi, yes.  When I was 18, I had an episode where I had pain in my left eye and lost vision rather abruptly.  By the time I saw my doctor, it had started to improve by itself and I did not think much of it."

Viola!!  Here the history is telling you that Miss Smith has in fact had  dissemination in time. Likely  she had an attack of optic neuritis when  she was 18 which had resolved by itself. So as a doctor examining Miss Smith, I  now know that her disease is disseminated in time (she has had  attacks in the past) and also in space (from my examination findings I know that she likely has multiple lesions in the brain, only then  I can explain all her findings).

I DO NOT NEED ANY ADDITIONAL TESTS TO MAKE A DIAGNOSIS OF MS. SHE HAS HAD 2 ATTACKS DISSEMINATED IN TIME AND SPACE. Of course as part of her management  I would do a  MRI study of the brain and some doctors might still do a lumbar puncture._  _

Additional tests like MRI brain, spinal tap and evoked potentials (visual and somatosensory evoked potential) are needed when either of the above 2 is missing_._ Either Miss Smith has had just one clinical attack or her examination findings are suggestive of a single lesion

There are however patients with whom history is either not contributory (they may have had only one attack) or with whom dissemination in space cannot be demonstrated either on clinical examination or on a MRI scan of the brain. In these patients we have to rule out other diseases. These include infectious diseases like Lyme disease, syphilis, disease like acute disseminated encephalomyelitis also called ADEM (here the etiology is thought to be either a preceding viral infection or vaccination),  connective tissue diseases like sarcoidosis, systemic lupus erythematosis (SLE) and various vasculitis may also resemble MS in their clinical presentation among numerous others.

_  _

So in patients with whom the diagnosis is not apparent, further tests including blood tests, examination of the spinal fluid and neuroimaging like CT scan and MRI scan may be needed to either rule in or rule out multiple sclerosis.

My own experience of seeing a neurologist for the first time included a wait of over three months.   In talking with other MS patients this  long wait  to be seen is not so unusual.   Can you tell us why it sometimes takes so long to get in to see a neurologist?

I often hear this complaint from patients. The delay in referral to a neurologist and hence diagnosis and timely treatment of MS may be because of multiple causes. The initial signs and symptoms of multiple sclerosis may be very non-specific and hence ignored by the patient. One example is isolated numbness in one arm or a short period of loss of vision in one eye (optic neuritis). Multiple sclerosis follows a relapsing and remitting course so symptoms may spontaneously remit and patients may not bother to follow up on them since they now feel better.

Doctor too may miss the significance of these initial non-specific signs of disease presentation. So in many patients the delay may occur because the initial symptoms were ignored or their significance was missed by a doctor.

Most insurances do not allow you to see a specialist directly, patients need a referral from their primary care doctor. A primary care doctor especially one who has not seen many MS patients in his practice may not think of multiple sclerosis as a possible differential diagnosis when a patient with non-specific symptoms presents to him. This may also cause a delay in timely referral to a neurologist.

Lastly small towns and cities frequently do not have a neurologist. Patients may need to travel long distances to see a neurologist in a university hospital. Appointments may be hard to come by adding further delay.

The adage "a stitch in time save nine" holds true for MS. The earlier the disease is diagnosed and treated with disease modifying therapies, the better is the outcome for the patient.

What symptom of MS is the most common one to bring a patient in to be checked on by a neurologist?

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.

  1. 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.

  1. 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.

  1. 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.

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

  1. 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.** Are there any predictors of which MS patients will have a better outcome as having less progression or disability over the years?**

There are certain predictors which guide us in prognostication purposes and answering patients questions about how their disease is going to play out. Unfortunately none of them are truly standardized and each patient's disease behaves slightly differently. If a patient at first presentation to me has extensive clinical involvement, is wheel chair bound, I know the disease is severe and likely to progress further. Some patients present with a clinically isolated syndrome and do not have a second attack for decades, these patients have what some doctors call "benign MS" though there is a debate among experts if there is actually anything like benign MS. Patients who have few lesions (plaques) on their MRI scan, absence of disease from the spinal cord, a low number on the expanded disability scale, good response to disease modifying drugs are the ones who usually have a better outcome.

**  I declined getting a spinal tap and was still able to be diagnosed.   If the neurologist has enough information to diagnose a patient with MS, why do they still ask patients to perform this sometimes painful test?** I think I answered this before but let me explain this again. As I stated earlier if you present with certain clinical signs and symptoms your doctor may entertain the diagnosis of multiple sclerosis. _Well if by history you have had two attacks suggestive of MS which are disseminated in time and space, then a definitive diagnosis of MS can be made. I _DO NOT NEED ANY ADDITIONAL TESTS TO MAKE A DIAGNOSIS OF MS. The problem arises when history of two or more attacks is lacking and the clinical examination or MRI scan is not suggestive of dissemination in space. The diagnosis now needs to be confirmed. __

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.

**  Do you believe that the Interferon medications delay the progress of this disease?   Which one do you feel works the best?**

Interferons act as disease modifying agents and delay the appearance of new lesions (plaques) in the brain. Nowadays we like to treat patients earlier in their disease course rather than later and also more aggressively. This is because studies have shown that damage occurs to the axons of the nerves early leading to disability. There are three different interferons in the market. One is interferon beta 1b marketed as Betaseron, the other is interferon beta 1 a marketed as Avonex and Rebif.

There is some data to show that high dose interferon beta 1 b (Betaseron) and beta 1 a (Rebif)   is better than Avonex   which is given once a week via an intramuscular injection. Other than that the choice of interferon or another medication called Copaxone is largely determined by the patient preferences (once a week intramuscular injection versus three times a week subcutaneous injections), side-effect profile and the treating doctors comfort level with the medication.

What would you recommend for treating the fatigue quite often present with Multiple Sclerosis?

Fatigue is a significant problem faced by most patients with multiple sclerosis. Patients at times may not mention this to their doctor during their visit. This is because they either do not relate the fatigue to MS or attribute it to side-effect of medications or their disability. Patients can do simple things by themselves to alleviate some of this fatigue. Frequent short rests between physical exertion helps. Heat has been noted to make physical fatigue worse. So working in a slightly colder ambient temperature is helpful. There are medications which can alleviate some of the fatigue. These include amantadine and Modafinil. So if you experience fatigue, take to your doctor about it.

Why do you think it is that more women than men end up having this disease?

That is an interesting question and one for which we still do not know the answer. The answer though probably rests in the genes which predispose us to this disease. I would like to add that MS is seen in men and there is some data to show that when it does occur in men it is frequently more severe.

What does the future hold for the patients who have MS?   Do you know of any promising medications or treatments coming down the pike?

I would like to end by giving hope to patients and care-givers alike. There is tremendous research being conducted in the field of MS.  Researchers are trying to study what sets up this cascade of immune destruction in the brain in some people and not in others. What makes one patient have severe disease and another a much milder variant? New drugs are in the pipeline as well as work being done trying to better understand how current disease modifying drugs work. The future in MS research looks promising and I am hopeful that some day we can overcome this chronic disabling neurodegenerative disorder.

**  I would love to ask you so many more questions.   I may save them for a subsequent interview if you are willing.   So for now...Any last thoughts**

Thank you for your questions. They were very thoughtful and I hope you find my answers equally insightful. I shall be happy to answer any more reader questions. I would like to end by thanking my patients and their families; they teach me something new very day and remind me why I entered this profession in the first place.