IgG4-related disease: neurologic manifestations
Nov. 29, 2022
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Approximately 25% of all children with an acute inflammatory demyelinating attack in the central nervous system will meet consensus criteria for a diagnosis of acute disseminated encephalomyelitis. Acute disseminated encephalomyelitis is clinically defined by polyfocal neurologic deficits and encephalopathy and is radiologically characterized by multifocal areas of increased signal in both white and gray matter of the brain and spinal cord visible on T2/FLAIR-weighted magnetization resonance images. Acute disseminated encephalomyelitis is primarily a pediatric disorder, though adults may also be affected. Though the etiologic mechanisms have not been fully elucidated, acute disseminated encephalomyelitis is thought to be an immune-mediated process and is often precipitated by preceding viral infection. Acute disseminated encephalomyelitis is typically a monophasic illness, but a multiphasic form, and relapses involving the optic nerves can occur, often in the context of myelin oligodendrocyte glycoprotein (MOG) antibody seropositivity. There are no laboratory features diagnostic of acute disseminated encephalomyelitis. Acute disseminated encephalomyelitis may be the presenting clinical attack for a small proportion of children ultimately diagnosed with a chronic demyelinating disorder such as multiple sclerosis, MOG antibody-associated disease, or neuromyelitis optica spectrum disorder. Features more strongly associated with monophasic acute disseminated encephalomyelitis are presented in this article. The authors discuss clinical and imaging features, etiology, differential diagnosis, and management of acute disseminated encephalomyelitis. Pathogenesis is also discussed, with updates focusing on the implications of myelin oligodendrocyte glycoprotein antibody seropositivity.
Acute disseminated encephalomyelitis is an inflammatory demyelinating disorder predominantly affecting white and gray matter in the brain and spinal cord.
Acute disseminated encephalomyelitis is more common in children than in adults.
Acute disseminated encephalomyelitis is thought to be an immune-mediated process that often follows viral illness.
Acute disseminated encephalomyelitis is clinically defined by encephalopathy and polyfocal neurologic deficits.
Approximately 50% of children with acute disseminated encephalomyelitis have serological antibodies against myelin oligodendrocyte glycoprotein at the time of initial presentation.
Acute treatment with corticosteroids is usually effective, and the course is typically monophasic.
Delayed neurologic complications after infections have been described since the 1700s. In the 1920s, pathologic differences between acute encephalitis and postinfectious encephalomyelitis were described, as were similarities between postinfectious and postvaccination (eg, rabies) encephalomyelitis. The first animal model of encephalomyelitis was produced in 1935 by Rivers and Schwentker by injecting monkeys with rabbit brain or spinal cord tissue; studies of this model suggested that delayed neurologic complications manifesting as encephalomyelitis following infections or vaccinations could result from sensitization of the immune system to proteins expressed by viruses (molecular mimicry) or by vaccines that contained proteins from neural tissue.
Early reports of postinfectious encephalomyelitis came from pediatric populations, following exanthematous infections. The term "acute disseminated encephalomyelitis" was introduced to describe any immune-mediated encephalomyelitis that resulted from infection, allergies, or vaccinations (59).
Historically, there has been inconsistent use and application of the term acute disseminated encephalomyelitis due to a lack of clear diagnostic criteria. As a result, the International Pediatric Multiple Sclerosis Study Group created an operational definition for acute disseminated encephalomyelitis in 2007, which was then updated in 2013. By definition, acute disseminated encephalomyelitis is an initial acute inflammatory event characterized by encephalopathy with polyfocal neurologic deficits occurring over a maximum period of clinical evolution of 3 months. MRI features include multifocal, large, and asymmetric areas of increased T2/FLAIR signal affecting the white and gray matter of the CNS (28; 29).
Although the requirement for encephalopathy in the definition of acute disseminated encephalomyelitis continues to be debated, it is considered essential by the consensus panel to avoid diagnosing every child with polyfocal MRI lesions with acute disseminated encephalomyelitis.
The International Pediatric Multiple Sclerosis Study Group redefined multiphasic disseminated encephalomyelitis in their 2013 consensus paper. Multiphasic disseminated encephalomyelitis is now defined as repeated episodes of demyelination that are separated by at least 3 months, with each episode meeting the definition of acute disseminated encephalomyelitis, and no evidence of either clinically silent lesion accrual on MRI or any other demyelinating attacks (attacks not meeting criteria for acute disseminated encephalomyelitis) (29). Children with initial event meeting criteria for acute disseminated encephalomyelitis, but who then experience repeated attacks that do not meet criteria for acute disseminated encephalomyelitis, should be evaluated for other disorders such as multiple sclerosis, MOG antibody-associated disease, neuromyelitis optica spectrum disorder, central nervous system vasculitis, or other etiologies.
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