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Geoepidemiology of Acute Disseminated Encephalomyelitis

Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

doi: 10.1097/EDE.0000000000000176
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Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, University Hospital Luigi Sacco, Università di Milano, Milan, Italy, sonia.radice@unimi.it

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To the Editor:

A cute disseminated encephalomyelitis is an inflammatory demyelinating disease of the central nervous system that may occur after viral illnesses or vaccinations.1

No information is available about the geographic distribution of acute disseminated encephalomyelitis, although several analyses (both clinical data2 and mouse–model response to ultraviolet radiation)3 suggest a correlation with latitude. The small size and specific regional setting of acute disseminated encephalomyelitis cohorts has hampered deep analysis of this relationship.

However, the association of latitude has been examined for multiple sclerosis, the most common central nervous system demyelinating disease.4 The risk of multiple sclerosis has been reported to increase from south to north, and several factors (including ultraviolet light exposure, genetic background, diagnostic accuracy, and ascertainment probability) can explain such distribution.4

The aim of this study was to evaluate whether acute disseminated encephalomyelitis has a demonstrable geographic distribution. As there is no indication of substantial changes in the incidence of this disease over time, we conducted this analysis considering the latest available information on the number of hospital admissions in the USA (2010 and 2011 National Inpatient Sample database) and in the UK (2012–2013 England’s Hospital Episode Statistics database).

We identified acute disseminated encephalomyelitis cases by searching the databases for any listed diagnosis classified with the appropriate ICD-9 and ICD-10 codes for this condition (323.61 and G040, respectively). States in the USA reporting 10 or fewer cases were excluded from analysis. Disease incidence was calculated using the population of each state as the denominator.

We calculated the Pearson correlation coefficients to examine the number of hospital admissions for acute disseminated encephalomyelitis in the USA and UK per year in relation to latitude. We found that disease incidence increased linearly with increased distance from the equator (r = 0.42; 95% confidence interval = 0.029–0.70) (Figure).

FIGURE

FIGURE

To confirm these results, we compared the incidence rates of acute disseminated encephalomyelitis among the various Census Bureau-designated regions in the USA. We found that the estimated incidence rates were considerably higher in the North-West of USA (latitude 33°–49° North; 0.38 cases per 10,000 inhabitants) than in South (latitude 26°–39° North; 0.22 cases per 100,000). Although these results could potentially be attributable to differences in population ethnicity, we did not find any correlation between race distribution and acute disseminated encephalomyelitis incidence, based on USA census bureau data.

This geographical distribution of acute disseminated encephalomyelitis is consistent with the previous analyses on the incidence of multiple sclerosis, which increases with the increasing distance from the equator in both the northern and the southern hemispheres.5

Several factors may explain the geographic pattern we reported here for acute disseminated encephalomyelitis, which cannot be attributed fully to diagnostic issues. As the most common antecedent factor leading to acute disseminated encephalomyelitis is infection,6 regional differences in the prevalence of infectious diseases and socioeconomic status may play a role in this distribution. A recent analysis highlighted the possible role of specific human leukocyte antigen alleles as risk factors for acute disseminated encephalomyelitis, which may account for a different distribution in the USA and other countries.7 As acute disseminated encephalomyelitis and multiple sclerosis are similar in terms of clinical and pathological features, it is reasonable to suppose that factors such as ultraviolet light exposure and vitamin D levels may be common to these pathologies.3

Despite the known limitations of discharge databases,8 we provide here the first evidence of a common geographical distribution between acute disseminated encephalomyelitis and multiple sclerosis. Further analyses are required to evaluate the incidence of acute disseminated encephalomyelitis at other latitudes and to evaluate the impact of other factors, including genetic predisposition.

Paolo Pellegrino

Sonia Radice

Emilio Clementi

Unit of Clinical Pharmacology

Department of Biomedical and

Clinical Sciences

University Hospital Luigi Sacco

Università di Milano, Milan, Italy

sonia.radice@unimi.it

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REFERENCES

1. Pellegrino P, Carnovale C, Perrone V, et al. Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems. PLoS One. 2013;8:e77766
2. Torisu H, Kira R, Ishizaki Y, et al. Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan. Brain Dev. 2010;32:454–462
3. Becklund BR, Severson KS, Vang SV, DeLuca HF. UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proc Natl Acad Sci USA. 2010;107:6418–6423
4. Goodin DS. The epidemiology of multiple sclerosis: insights to disease pathogenesis. Handb Clin Neurol. 2014;122:231–266
5. Wender M. Acute disseminated encephalomyelitis (ADEM). J Neuroimmunol. 2011;231:92–99
6. Tenembaum SN. Acute disseminated encephalomyelitis. Handb Clin Neurol. 2013;112:1253–1262
7. Alves-Leon SV, Veluttini-Pimentel ML, Gouveia ME, et al. Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study. Arq Neuropsiquiatr. 2009;67:643–651
8. Pellegrino P, Carnovale C, Perrone V, et al. Epi demiological analysis on two decades of hospitalisations for meningitis in the United States. Eur J Clin Microbiol Infect Dis. 2014;33:1519–1524
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