It's almost lunchtime. You've seen a steady stream of patients throughout the morning, most of whom just had seasonal flu. "I'll be sending in the last patient now", your nurse says. ".... and then I can have lunch", you think.
Susan, a 26-year-old postgraduate student looks visibly frightened. "Doctor! My eyes started hurting when I woke up today. Everything seems blurred and all colors are off!".
Her words make you sit up straight. Feeling concerned, you ask several follow up questions. This is the first time Susan has experienced these symptoms. Close questioning reveals that she has been feeling tired and fatigable for the last 2 weeks. No other symptoms are present. She has been in perfect health until now and is not on any medications, including over-the-counter drugs, herbal medications, or supplements. Her family history is unremarkable. She only drinks socially and has never smoked or used recreational drugs.
On inspection, both eyes look normal. However, the pupillary light reaction appears to be diminished in the right eye, while visual acuity is 20/30 in the left eye but only 20/50 in the right eye. Confrontation, ocular motility testing, and fundoscopy are all normal. The remainder of the examination is also normal.
Feeling even more concerned, you write out an urgent referral to the ophthalmology clinic and ask Susan to go there and come back to your office once done. While she is away, you take the opportunity to gulp down a quick lunch.
Almost two hours later, Susan is in front of you once more. You quickly review the results of the ophthalmology referral. Slit lamp examination showed no abnormalities. However, perimetry revealed a central scotoma and altitudinal and arcuate defects of the visual field of the right eye.
The ophthalmologist took it on himself to order an urgent cranial MRI as well. This showed a demyelinating plaque of the right optic nerve. His diagnosis is optic neuritis, and he has started Susan on a course of corticosteroids. She will be admitting herself to the hospital once done speaking to you.
"Thank you so much, doctor. The ophthalmologist explained everything, and stressed that I'm lucky that we caught the problem so quickly", Susan says. "But I didn't quite understand one thing - what exactly is the disease I have?"
"You probably have -", you say and suddenly stop as your latent knowledge asserts itself.
"Well, all we can say is that your optic nerve is inflamed. This isn't any more a diagnosis than, say, 'a fever' or 'a cough' is", you say and continue, "We just don't have enough information to identify what the underlying condition might be".
"What will you do then, doctor? Will you be running any more tests?", she asks.
You are about to open your mouth, but something gives you pause. After a little thought, you recall the conclusions of the Optic Neuritis Treatment Trial (ONTT). In the ONTT, testing patients with optic neuritis for antinuclear antibodies, syphilis serology, and chest x-rays were found to be of no therapeutic consequence; meticulous history-taking followed by targeted laboratory testing was recommended instead.
"I'm afraid that further testing wouldn't be helpful right now. All we can do is to treat your eye problem and keep a careful watch out for symptoms in the future". You proceed to explain about demyelinating diseases, and what signs and symptoms she should be on the watch for.
Susan thanks you and prepares to take her leave. As the ophthalmologist will be treating the optic neuritis directly, you ask her to continue the follow-up with him once discharged from the hospital, but to also drop into your clinic if she experiences any other symptoms.
A year passes. You have just started your clinic again, and the first patient is sent in. You look up to see that it is Susan.
"Doctor! You've got to help me. I've been passing urine without realizing it for the past week, but I thought that it might be due to overwork or stress. Today though, when I bend my head forward, I feel a shock running down my back and limbs!", she says in a frenzy.
"Ok, calm down Susan - let's look at what happened", you say soothingly while thinking "... sounds like Lhermitte's sign". You find out that she has no other symptoms. Her vision has recovered just fine, without MRI evidence of demyelination several months after the course of corticosteroids. All other components of her history remain unchanged.
You proceed to perform a careful neurological examination. This reveals generalized weakness of the left lower limb (strength 4/5 in all muscle groups), and a positive Babinski sign in both limbs. The remainder of the examination is unremarkable.
You order an urgent cranial and spinal MRI, and call the radiologist to mention your concerns. You also inform Susan that she needs admission, and make the necessary arrangements.
During your ward round in the afternoon, you look at Susan's MRI report. This reveals two demyelinating plaques in the lumbar spinal cord, and multiple bilateral periventricular plaques in the brain. You realize that her clinical picture is now diagnostic of multiple sclerosis. Multiple sclerosis is challenging to treat, requiring a highly individualized discussion between the patient and the doctor about the potential benefits and risks of each option, within the context of the patient's disease course. After explaining this to Susan, you ponder the best course of treatment.
You consider starting Susan on corticosteroids and interferon-beta-1a simultaneously, but something doesn't feel right. A quick look at your medical reference shows that initial corticosteroid therapy will help relieve symptoms and reduce the duration of relapse; interferon-beta-1a therapy can be subsequently started as a disease-modifying agent.
You consider starting Susan on interferon-beta-1a alone, but decide to ask the head of the department for his opinion first. "No. Corticosteroids will shorten the severity and duration of the relapse; we can then start interferon as a disease-modifying agent", he says.
You start Susan on high-dose IV corticosteroids for three days. Towards the end of the course, her condition has markedly improved. Her left limb returns to normal strength, although the Babinski signs remain positive bilaterally.
Subsequently, you start her on interferon-beta-1a via the intramuscular (IM) route. Afterward, you send her home with instructions on how to administer the medication properly, and schedule regular follow-up visits.
At her 3-month follow up, Susan is accompanied by her husband, Erik. She has been administering herself IM interferon-beta-1a each week, without adverse effects. Her Expanded Disability Status Scale (EDSS) is 1.0, as the Babinski signs continue to remain positive.
"Doctor, I've been feeling a strange sensation on the left side of my face. It feels like it's wet, even when it's not wet!", she says.
Her history has no other significant symptoms, and the neurological examination only reveals positive Babinski signs on both sides, as it has all this time. There are absolutely no sensory abnormalities.
"Let's do an MRI again", you tell her and write out the relevant order. You schedule a follow-up consultation to review the MRI results.
The following day, Susan and Erik are back in front of you. The MRI shows that the old plaques in the lumbar spine and brain continue to persist and that there are multiple new plaques in the cerebral cortex.
You consider increasing the interferon-beta-1a dose, but realize that this isn't the best course of action.
You consider adding corticosteroids, but realize that this isn't the best course of action.
You inform Susan that a new plaque has appeared and that taking into account her clinical history, it is likely that she has relapsing-remitting multiple sclerosis. Therefore, you'll be starting her on a new drug: natalizumab. You proceed to explain the rationale for natalizumab in detail and the risks versus benefits. You also educate her about the potential adverse effects and what she should be looking out for.
"I read about this drug earlier, doctor", Erik says, and continues, "I guess that you'll be screening her before starting treatment?"
"No, we don't need to screen her", you respond. Erik looks confused. "But doctor, I read that she needs to be screened for a JC virus or something like that?", he asks. You realize that he is right!
"Quite right. We need to screen her for hepatitis B and tuberculosis", you respond. Erik looks confused. "But doctor, I read that she needs to be screened for a JC virus or something like that?", he asks. You realize that he is right!
"Yes. We must screen her for Polyomavirus JC first. If the test reveals antibodies to that virus (i.e. anti-JCV antibodies) she will be at increased risk of developing multifocal leukoencephalopathy, a very serious complication", you respond.
You proceed to write out the relevant test and ask Susan and Erik to come back in a few days, once results are available.
Several days later, the test results are in. Susan is negative for JCV antibodies, and you immediately start her on natalizumab every 4 weeks.
At the 6th month of therapy, Susan and Erik are back to your office for her usual follow up. She has responded well to the therapy. Her EDSS is still 1, and she has not experienced any adverse effects.
You also re-ordered MRI imaging. This shows a 20% improvement of the lesion load. "You're doing good!", you say, and proceed to give her the results of the imaging studies, and that she should be optimistic about the future. Both Susan and Erik look very happy on hearing this, and cannot stop thanking you.