Multiple sclerosis: making the diagnosis

So let us start from where we left off. Just how do we (doctors) go about making (confirming) the diagnosis of MS.

MRI scan: Well one of the test most commonly requested (infact done in nearly every patient) is a MRI scan of the brain and at times of the cervical spinal cord. What are we looking for you may ask? Well multiple sclerosis on the MRI is characterized by plaques (lesions) which are disseminated in space and in time. What does that mean? In a typical patient of MS, the MRI scan shall show evidence of disease activity which is scattered around in different parts of the brain. Meaning there are MS lesions seen in different parts of the brain white matter (typically MS is a white matter disease though recent research indicates involvement of the grey matter too). So for example a typical MRI scan shall show plaques scattered  in the white matter of the frontal lobe, parietal, temporal lobe, cerebellum and so forth. Moreover the MRI scan shall indicate that these plaques are of different age (which indicates that the disease has been present for sometime now). Remember what I said –relapsing and remitting MS. Sometimes to help secure the diagnosis, your doctor shall also order a MRI scan of the spine most commonly cervical spine. The intention is the same and that is to see evidence of dissemination of the disease process in the brain and spinal cord.

Spinal tap: a lumbar puncture is usually carried out. Does every patient need a spinal tap to help secure the diagnosis of MS? No. Remember the diagnosis of MS can be made clinically in some patients. In patients where the characteristic history is not forthcoming and in whom the MRI scan does not prove helpful (does not evidence of dissemination of disease process in space and time), a spinal tap may be warranted.  The spinal fluid of MS patients is analyzed for certain proteins which suggest evidence of disease process. These include myelin basic protein (MBP), oligoclonal bands (OCBs) and IgG index.

Other tests: these tests may be requested in special circumstances (usually when the diagnosis remains elusive inspite of MRI scans and spinal tap).

1) Visual evoked potential (VEP), brainstem auditory evoked potential (BAEP) and somatosensory evoked potentials (SSEP):  these tests usually involve testing the integrity of different pathways in the brain. VEP tests the visual pathway from the eye to the occipital (visual) cortex, BAEP–tests the brainstem auditory pathways while SSEP check for the integrity of the white matter tracts carrying somatosensory information (vibration, joint sense and position sense) from the periphery (arm or leg) to the somatosensory cortex.  MS lesions involving any of these pathways cause a delay in the rate of conduction of nerve impulse and provide ancillary evidence of involvement of white matter tracts of the brain by a demyelinating disease process.

I hope these two posts help you all in understanding how the diagnosis of MS is made.


Nitin Sethi, MD

Multiple Sclerosis–making the diagnosis

I still continue to get many questions from the readers of my blog regarding multiple sclerosis (MS). A significant majority of them write to me because they are concerned they may have MS either because of white matter lesions found on a MRI scan of the brain or because they are plagued by various non-specific signs and symptoms. Though I have written about this before, I thought this shall be a good time to go over how the diagnosis of MS is made. What are the symptoms that raise the suspicion for MS, what are the clinical signs on examination that suggest MS and finally what are the tests that may help to confirm the diagnosis.

Before I dwell deeper into this topic, please remember: THE DIAGNOSIS OF MS IS A CLINICAL ONE. Meaning that it can be made on the basis of a history and clinical examination itself. No tests are needed in such a situation to confirm the diagnosis.  Of course as it is often in medicine–it is always not that easy.

So let us begin—

Clinical history: Are there any points in the clinical history of the patient that suggest the diagnosis of MS? Patients with MS may give a history of neurological symptoms and signs (remember signs are elicted on clinical examination-meaning when the doctor examines you) that wax and wane (relapsing and remitting MS). A patient may present with acute loss of vision in one eye along with pain in the eye  (I am talking about optic neuritis). As the doctor dwells deeper into the history, the patient volunteers that a couple of years ago he had a similar problem in the other eye which had resolved on its own and he had not been investigated further. Hmmm–now we have history of 2 attacks separated in time. As a neurologist this makes me think of MS as a possible diagnosis. The problem with MS though is that it may present with non-specific signs or symptoms or rather it may present with signs and symptoms that localize to different parts of the central nervous system (CNS). By CNS I mean the brain and the spinal cord. So for example patients may present with numbness on weakness on one side of the body (this localizes to the contralateral motor or sensory cortex), problems with the bladder (incontinence–this usually localizes to the spinal cord), problems with balance and coordination (their gait is off and they may have a prominent tremor in their limbs–this localizes to the cerebellum or the brain stem), double vision (this localizes to the cranial nerves which control the movement of the eyes). Virtually any part of the central nervous system can be involved–hence the presentation is at times non-specific. BUT WHAT HELPS US AS DOCTORS IS WHEN WE GET HISTORY WHICH SUGGESTS A DISEASE DISSEMINATED IN SPACE AND IN TIME. Meaning a disease process which is involving different parts of the central nervous system and which has shown evidence of multiple attacks separated by time. REMEMBER MS IS NOT A MONOPHASIC ILLNESS (it relapses and remits!!!)

Clinical examination: So what are the clinical examination findings which make me as a neurologist think of MS in  a patient. There are certain neurological signs which have been said to be pathogonomic of MS (meaning the presence of these signs virtually seals the diagnosis of MS). These include certain eye signs. Bilateral internuclear opthalmoplegia (INO) (who said neurology was easy!!!) is one such sign. This is an eye-sign in which the patient’s eyes do not move as directed by the examiner. One eye fails to adduct (that is move inwards) while the other eye  abducts (moves outwards) but the abducting eye shows a nystagmus (shaky side to side movement). Other eye signs such as an afferent pupillary defect (this is elicted by shining a penlight into the eye) also raise suspicion for MS. What we as neurologists look for though is this–we look for signs that suggest the disease is disseminated in the CNS. REMEMBER WHAT I TOLD YOU ABOUT MS. IT IS A DISEASE WHICH IS DISSEMINATED IN TIME AND SPACE.

Tests: so when a diagnosis of MS cannot be made on the basis of history and examination alone, we as doctors have to fall back on tests to rule in or rule out the diagnosis. No test seals the diagnosis of MS by itself. They just help to add to our certainity. I shall discuss the various tests namely –imaging studies such as MRI scan of the brain and spinal cord., evoked potential studies such as visual evoked potential (VEP), somatosensory evoked potential (SSEP), brain stem auditory evoked potential (BAEP), spinal fluid (CSF) examination in the next post.


Nitin Sethi, MD

Multiple Sclerosis-a question and an answer

 One of readers emailed me this question. My response to it follows.

Riddler on October 17, 2008 said: Edit Link

Hello Dr,

I am a 28 asian/indian female. I was brought up in India for large part of my file.
I had symptoms of blind spots in my vision sometime back. The condition persisted for 2 days before I scheduled an appointment with my opthamalogist. He suspected that I have optic nueritis and advised me for a MRI. Now the lab technician says that I have a few lesions in my brain and asked me to consult a nuerologist. I have a pending appointment. My eye became completely normal in about 10 days from onset. By googling I found that it might be a case of MS.

Is it always the case optic nueritis + MRI lesions = MS? Is there anything else I should be looking at? I’ve had problems of vitamin deficiencies in the past. I have had some tongue rashes, gastro problems. Nothing serious but minor issues though.


Dear Riddler,

                                      patients who have optic neuritis usually do not complain of blind spots, rather they have acute/sudden loss of vision (usually in one eye, though in a condition called neuromyelitis optica they may have optic neuritis in both eyes). This condition may be painful (complaint of pain in the eye). Not all patients who have optic neuritis have multiple sclerosis. There can be many other causes of optic neuritis namely other infectious and inflammatory conditions. Patients who present with optic neuritis and are in the right age group (eg a woman in her 20s or 30s presenting with optic neuritis), need to be worked up for multiple sclerosis. Usually we order a MRI brain, to see if there is evidence of multiple sclerosis (read my posts on white matter lesions in the MRI brain of MS patients at As I have stated repeatedly, not all white matter lesions on the MRI represent multiple sclerosis.

In answer to your question, yes some vitamin deficiencies can cause blind spots and lesions in the brain. My advise to you would be to see a neurologist, the diagnosis of optic neuritis can be confirmed with the aid of certain tests like visual evoked potentials (VEP). Then the MRI can be interpreted in the right context.

Personal Regards,

Nitin Sethi, MD