Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) of autoimmune origin. Focal demyelination of the brain, spinal cord and optic nerves leads to progressive loss of neuronal and axonal integrity and thus disability. Some patients with MS may have atypical demographics or presentation, both clinical and radiological may have atypical features.
It is now well recognized that not all demyelinating diseases are the same. Some patients who were previously labelled as “opticospinal MS” are now known to have a different disease mediated by Aquaporin4 (AQP4) antibodies, called neuromyelitis optica spectrum disorder (NMOSD). Recently a further sub-group of patients with both monophasic and relapsing disease has been recognized with myelin oligodendrocyte glycoprotein (MOG) antibodies. This condition, like AQP4 disease, is phenotypically distinct from MS.
Classification of these demyelinating conditions has been predicated on advances in immunologic assays. However, the classification of other atypical demyelinating diseases has been based on clinical and radiological features with some overlapping manifestations. Consequently, accurate diagnosis can be complex and long-term follow-up may be required for clarifying the diagnosis. In patients with non-MS phenotypes who are negative for the known autoantibodies, other inflammatory (e.g systemic inflammation) or non-inflammatory (e.g inherited white matter disorders) etiologies should be considered. The proportion of all demyelinating diseases represented by atypical variants differs among populations, with a larger share of atypical variants seen in pediatrics and certain non-Caucasian geographic regions, for example NMOSD in East and South Asia.
Molecular autoantibody diagnosis has not only led to refined diagnostic algorithms but has also transformed estimates of the prevalence of these diseases and appropriate resource allocation. Demographic characteristics like age, sex, and ethnicity play an important role in determining risk factors and may affect prognosis. For example, some studies have shown that relapse types and recovery vary substantially in NMOSD by age and ethnic background. Knowledge of these risk factors can assist with diagnosis and treatment decision-making, particularly as new treatments become available.
Finally, atypical demyelinating diseases are acquired illnesses, presumably triggered by environmental exposure on a background of genetic vulnerability. Environmental factors that may contribute to demyelinating diseases include smoking, vitamin D status and sun exposure, obesity, infections, and vaccination. There may be environmental factors unique to certain disorders, for example the suggestion made in a recent finding that a Clostridium species was overrepresented in the gut microbiota of NMOSD subjects. Genetic risk factors and gene-environment interactions require further study, ideally using multi-national cohorts with a wide representation of haplotypes.
In this Research Topic, we welcome original research, review papers, case reports and viewpoint pieces concerning the epidemiology of atypical demyelinating diseases. These include NMOSD, MOG antibody disease, acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis, tumefactive demyelinating disease, and Balo’s concentric sclerosis. Any of the following manuscript types would be welcome:
- Prevalence and incidence studies;
- Natural history studies;
- Studies of environmental risk factors;
- Genetic studies;
- Studies of prognostic factors;
- Studies of co-morbid conditions.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) of autoimmune origin. Focal demyelination of the brain, spinal cord and optic nerves leads to progressive loss of neuronal and axonal integrity and thus disability. Some patients with MS may have atypical demographics or presentation, both clinical and radiological may have atypical features.
It is now well recognized that not all demyelinating diseases are the same. Some patients who were previously labelled as “opticospinal MS” are now known to have a different disease mediated by Aquaporin4 (AQP4) antibodies, called neuromyelitis optica spectrum disorder (NMOSD). Recently a further sub-group of patients with both monophasic and relapsing disease has been recognized with myelin oligodendrocyte glycoprotein (MOG) antibodies. This condition, like AQP4 disease, is phenotypically distinct from MS.
Classification of these demyelinating conditions has been predicated on advances in immunologic assays. However, the classification of other atypical demyelinating diseases has been based on clinical and radiological features with some overlapping manifestations. Consequently, accurate diagnosis can be complex and long-term follow-up may be required for clarifying the diagnosis. In patients with non-MS phenotypes who are negative for the known autoantibodies, other inflammatory (e.g systemic inflammation) or non-inflammatory (e.g inherited white matter disorders) etiologies should be considered. The proportion of all demyelinating diseases represented by atypical variants differs among populations, with a larger share of atypical variants seen in pediatrics and certain non-Caucasian geographic regions, for example NMOSD in East and South Asia.
Molecular autoantibody diagnosis has not only led to refined diagnostic algorithms but has also transformed estimates of the prevalence of these diseases and appropriate resource allocation. Demographic characteristics like age, sex, and ethnicity play an important role in determining risk factors and may affect prognosis. For example, some studies have shown that relapse types and recovery vary substantially in NMOSD by age and ethnic background. Knowledge of these risk factors can assist with diagnosis and treatment decision-making, particularly as new treatments become available.
Finally, atypical demyelinating diseases are acquired illnesses, presumably triggered by environmental exposure on a background of genetic vulnerability. Environmental factors that may contribute to demyelinating diseases include smoking, vitamin D status and sun exposure, obesity, infections, and vaccination. There may be environmental factors unique to certain disorders, for example the suggestion made in a recent finding that a Clostridium species was overrepresented in the gut microbiota of NMOSD subjects. Genetic risk factors and gene-environment interactions require further study, ideally using multi-national cohorts with a wide representation of haplotypes.
In this Research Topic, we welcome original research, review papers, case reports and viewpoint pieces concerning the epidemiology of atypical demyelinating diseases. These include NMOSD, MOG antibody disease, acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis, tumefactive demyelinating disease, and Balo’s concentric sclerosis. Any of the following manuscript types would be welcome:
- Prevalence and incidence studies;
- Natural history studies;
- Studies of environmental risk factors;
- Genetic studies;
- Studies of prognostic factors;
- Studies of co-morbid conditions.
