Barts-MS rose-tinted-odometer – zero stars
We ran our third triMS-online this week and apart from a technical problem in the satellite symposium it went reasonably smoothly. The participants were very engaged and asked lots of questions. The topic of vaccination was particularly well received. Which vaccine? Component or live vaccines? When to give the vaccines and whether or not to delay starring a DMT to complete the schedule.? Interestingly and importantly MMR, or mumps, measles and rubella, was not on the radar.
It is my impression that the MS community assume these childhood infections and vaccinations are done and dusted. However, with the rise of the anti-vaccine movement, there is an increasing number of people not being vaccinated in childhood with the MMR. This means that an undefined number of pwMS will be MMR seronegative. Is this a problem? You bet it is!
To explain the consequences of getting measles infection as an adult on immunosuppression I penned this fictional case scenario. According to the “Donald Rumsfeldometer”, this is an unknown known.
- Known-knowns – there are things we know that we know
- Unknown-knowns – these are the things we know will occur
- Known-unknowns – there are things that we now know we don’t know
- Unknown-unknowns – there are things we do not know we don’t know
“There are known knowns; there are things we know that we know. There are known unknowns; that is to say, there are things that we now know we don’t know. But there are also unknown unknowns – there are things we do not know we don’t know.”
Donald Rumsfeld, former United States Secretary of Defense.
When she finally arrived on the ward she was unable to speak and was clearly confused and disorientated. All four of her limbs were twitching and would jerk when touched; i.e. she had generalised myoclonus. She was drooling from the mouth. Her latest MRI showed hyperintense signal change in the cortical ribbon or the grey matter on the surface of her brain.
Since her last MRI 8 days ago, the involvement of cortex had spread from the left parietal lobe to involve the entire left frontal lobe, the medial surface of the right frontal lobe, the left occipital lobe and the left temporal lobe. There was new signal change in the left thalamus and pulvinar and the white matter of the left hemisphere was diffusely involved. Interestingly, the post-contrast scans showed no obvious gadolinium-enhancement. Her EEG showed diffuse slowing over the left hemisphere with occasional sharp waves. The neurophysiologist did not think the pattern was a burst suppression pattern.
She was only 24 years of age and had been on natalizumab for 37 months. She was JC virus seronegative and her most recent CSF examination was negative on PCR for JC virus DNA. Apart from a mildly raised protein, the CSF was acellular. Her referring neurologist thought the most likely diagnosis was a secondary CNS lymphoma and had referred to our centre for a brain biopsy.
What the neurologist had missed was that this patient had recently come into contact with her friend’s 4-year old daughter who had been diagnosed with measles. In fact, there had been a cluster of eight cases of measles in the nursery school her friend’s daughter had attended. The tragedy is that this patient had not received her MMR vaccine as a child because her mother had been concerned about the safety of the MMR vaccine after the now retracted and fraudulent Andrew Wakefield study linking MMR vaccine to autism.
Once we had this history our working diagnosis was that of a measles inclusion body panencephalitis and our diagnosis was confirmed once we got back the CSF measles PCR result from her repeat lumbar puncture. Sadly the patient passed away 5 days after admission. A post-mortem examination confirmed the diagnosis of measles inclusion-body panencephalitis.
Interestingly, despite being on natalizumab there were was quite a heavy CD8+ T-cell infiltrate, which would indicate that natalizumab does not necessarily block all trafficking of lymphocytes into the brain of someone with viral encephalitis.
So if you have MS and are about to start an immunosuppressive DMT please review your vaccine history. If you discover you have not had the MMR vaccine or other vaccines you may need, please discuss this with your neurologist or MS nurse. Once you are on specific DMTs live vaccines such as the MMR are contraindicated.
I am sure some of you will be saying that I am scaremongering, but I know that it is only a matter of time before we see MMR-naive patients with MS succumb to wild-type or community-acquired infection with one or more of these viruses (see case study below).
Please note measles and mumps are circulating at present in the community and because of lower rates of MMR vaccine uptake you can’t necessarily rely on herd immunity to shield you from infection.
Isn’t prevention better than managing the consequences of these infections?
Freeman et al. A new complication of stem cell transplantation: measles inclusion body encephalitis. Pediatrics. 2004 Nov;114(5):e657-60.
Measles inclusion body encephalitis (MIBE) is a disease of the immunocompromised host and typically occurs within 1 year of acute measles infection or vaccination. We report a 13-year-old boy who had chronic granulomatous disease and presented 38 days after stem cell transplantation with afebrile focal seizures that progressed despite multiple anticonvulsants. After an extensive diagnostic evaluation, brain biopsy was performed, revealing numerous intranuclear inclusion bodies consistent with paramyxovirus nucleocapsids. Measles studies including reverse transcriptase-polymerase chain reaction and viral growth confirmed measles virus, genotype D3. Immunohistochemistry was positive for measles nucleoprotein. Despite intravenous ribavirin therapy, the patient died. MIBE has not been described in stem cell recipients but is a disease of immunocompromised hosts and typically occurs within 1 year of measles infection, exposure, or vaccination. Our case is unusual as neither the patient nor the stem cell donor had apparent recent measles exposure or vaccination, and neither had recent travel to measles-endemic regions. The patient had an erythematous rash several weeks before the neurologic symptoms; however, skin biopsy was consistent with graft-versus-host disease, and immunohistochemistry studies for measles nucleoprotein were negative. As measles genotype D3 has not been seen in areas where the child lived since his early childhood, the possibility of an unusually long latency period between initial measles infection and MIBE is raised. In addition, this case demonstrates the utility of brain biopsy in the diagnosis of encephalitis of unknown cause in the immunocompromised host.