Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis (ADEM). Acute perivenous demyelination of brain and spinal cord. Usually a monophasic disease, i.e. unlike multiple sclerosis, no further recurrences or relapses are expected.
There is a hyperacute form known as acute hemorrhagic leukoencephalitis (AHLE).
Presumed auto-immune. Frequently occurs in a post-infective or para-infective time frame, e.g. following childhood exanthema such as chickenpox and measles, and also after certain upper respiratory tract infections. ADEM It has also been associated with conditions such as HIV and other infections.
ADEM has also been linked to vaccination, but this link is rather tenuous.
ADEM is probably not caused by vaccination
ADEM seems to be a rare condition seeking a cause.
The evidence that ADEM is linked to vaccination is extremely tenuous, largely based on uncontrolled and isolated case reports. Case reports are very susceptible to confirmation bias, and do not distinguish between observed and expected rates: their place is in hypothesis generation, not hypothesis testing.
Many of the articles suggesting links with vaccination are rather old, and refer to very small (or single) numbers of cases. As humans (and physicians) we like to look for causes and effects, and tend to assume that association = causation. ADEM typically occurs in childhood, so it would not be unusual – by chance – for there to be a temporal association with vaccination. One can well understand that clinicians, trying to explain an interesting moderately serious (though most cases make a full recovery), and very rare condition will try hard to identify a “cause”, and clutch at the straw of a recent vaccination. The condition is probably too rare for us to be able to say with certainty if there is a genuine link or not, although perhaps work with very large linked datasets (GPRD?) might throw some light on this.
There is insufficient evidence to support the hypothesis that there is a causal link between ADEM and vaccination.
A quick PubMed search finds several case reports of ADEM following vaccination, e.g.
- Sekiguchi et al two cases, presenting 14 and 16 days after HPV vaccination (in Japan).
- Letter, single case report of ADEM “secondary” to serogroup B meningococcal vaccine (“The incidence in the adult population has not been precisely established; it is estimated that < 5% of all cases arise after antigenic vaccination. The vaccines most frequently linked to this disease are MMR (measles, mumps, and rubella), influenza, rabies, and tetanus.”). By using the term “secondary” it makes me doubt the epidemiological knowledge of the authors – clearly, [temporal] association =/= causation…
- A systematic review of 6 studies, which found some cases or possibly only one case - of ADEM (and also cases of other autoimmune diseases) associated with yellow fever vaccine.( citing )
- A rather better quality article in Vaccine which says, re ADEM (ignore citations in quote):
- “Of 250 publications of ADEM reviewed, nine studies met the inclusion criteria, were deemed to be potentially informative, and were assessed in their entirety for any report of ADEM onset following immunization , , , , , , ,  and . Eight of these studies had provided information on ADEM onset following natural infection. In these studies, the smallest and largest mean values of the interval between the onset of natural infection and neurologic symptoms and signs were 6.2 and 17.8 days, respectively (Fig. 2). Only two studies had explicitly indicated the timing of ADEM onset following immunization. The first study by Torisu et al. was a multicenter population based study of ADEM among 26 children 15 years of age and younger in Japan . Four vaccine-associated cases following Japanese encephalitis, rubella, hepatitis B, and live poliovirus vaccines were identified. The mean onset of ADEM following immunization was 17 days (range: 9–30 days). The second study by Hynson et al. was a retrospective review of medical records from 31 children with ADEM 16 years of age and younger in Australia . Two cases had received the hepatitis B vaccine 3–6 weeks before the ADEM onset. Finally, the VAERS review did not show a notable clustering of cases (n = 56); however, the mode of the distribution occurred on days 11 and 12 (4 cases on each day).”
- A single case following MMR vaccination.
- A more recent publication, which states in the Results section:
- Results. Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5–28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the odds ratio for Tdap exposure 5–28 days prior to ADEM onset was 15.8 (95% confidence interval [CI], 1.2–471.6; P = .04), and the estimated excess risk was 0.385 (95% CI, −.04 to 1.16) cases per million doses.
- Conclusions. We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered.
- This association is not very convincing - with only 2 cases the numbers are very small, and the P value is only just below 0.5. It is not impossible that there may have been elements of bias (confirmation and publication bias) in identifying these cases.
- May present with neuropsychiatric symptoms
- Headache, vomiting, confusion, meningism
- Pyrexia (uncommon in adults)
- Focal/multifocal brain and spinal cord signs
- Seizures are not common as the lesions are subcortical
- Flaccid paralysis + extensor plantars
- Cerebellar signs (esp. post chickenpox)
- MRI – multiple high signal areas (multifocal subcortical white matter lesions)
- CSF – Normal or increased mononuclear cells and protein; may show oligoclonal bands.
- Can be fatal
- Immunosuppresion, e.g. intravenous methylprednisolone