Learn more about other demyelinating diseases that affect children:
What is ADEM?
Acute disseminated encephalomyelitis (ADEM) is an inflammatory disorder of the central nervous system which predominantly affects the white matter of the brain, spinal cord and optic nerves. It is usually triggered by an infection or vaccination.
ADEM is sometimes difficult to distinguish from multiple sclerosis (MS) because the symptoms common to both “demyelinating” disorders include loss of vision, weakness, numbness and loss of balance. Both ADEM and MS involve immune-mediated responses to myelin in the brain and spinal cord.
Who gets ADEM?
ADEM can occur at any age, but it is more common in children than in adults. The mean age at presentation is from 5 to 8 years old. Both boys and girls can be affected, butt it seems that there is a male predominance with female to male ratios of 0.6 and 0.8.
The mean incidence of ADEM is 0.4/100,000 a year in children. A seasonal distribution in the winter and spring has been found in studies.
Signs and Symptoms of ADEM
Neurological signs and symptoms appear days to weeks after an infections or vaccination with an average latency of 4 to 13 days. Symptoms often include fever, headache, vomiting, lethargy and irritability. The initial neurologic symptoms are generally multifocal and determined by the location of the lesions within the CNS. These most commonly include altered level of consciousness (encephalopathy), pyramidal tract dysfunction including paralysis of one extremity (or part of one extremity, such as hands or feet), paralysis affecting one side of the body, uncoordinated movement and brainstem dysfunction including cranial nerve palsies and optic neuritis. Other clinical features include seizures and meningeal signs.
Diagnosis of ADEM
Diagnosis of ADEM is based on the clinical presentation, investigations including spinal fluid studies and MRI findings.The spinal fluid may show elevated protein levels. MRI brain shows multifocal, poorly bordered cerebral white matter lesions that enhance with gadolinium. The lesions are usually large, asymmetric and can involve the subcortical and central white matter and cortical gray-white junction of the cerebral hemispheres, cerebellum, brainstem and spinal cord.
Treatment of ADEM
There is no standard therapy for ADEM. Current treatment approach is based on non-specific immunosuppression with intravenous steroids followed by oral prednisone taper. Other immunomodulatory therapies including IVIG or plasmapheresis are used in cases refractory to steroids. Supportive therapy and symptomatic treatment of associated symptoms such as seizures is important.
Research in ADEM
ADEM often poses a diagnostic and prognostic challenge for neurologists. One of the most pressing questions of a child presenting with ADEM is the future risk for conversion to MS. Identification of a biomarker that will help predict the development of MS after an ADEM event is critical. There is ongoing research to understand the worldwide epidemiology and distribution of ADEM. These studies will help to gain insight into the pathogenesis of ADEM and potential preventative measures.
What is NMO?
Neuromyelitis optica (NMO), also known as Devic’s disease, is an autoimmune disorder in which immune system cells and antibodies mistakenly attack and destroy myelin cells in the optic nerves and the spinal cord. The damage to the optic nerves produces swelling and inflammation that cause pain and loss of vision; the damage to the spinal cord causes weakness or paralysis in the legs or arms, loss of sensation, and problems with bladder and bowel function.
NMO occurs in two different forms: a single attack extending over a month or two, or a more common relapsing form in which the person experiences multiple attacks.
Who gets pediatric NMO?
Current studies suggest that approximately 3% of all NMO patients experience their first symptoms in childhood or adolescence. Patients as young as 16 months have been reported with NMO. The average age for children is 10 years old. Both boys and girls can be affected, but like in adults, there is a female bias at approximately 2:1.
Symptoms of pediatric NMO
Children with NMO usually present with “attacks” of new neurological symptoms appearing within a few hours or days. Children with NMO can have attacks with symptoms of blurred vision, or loss of vision in one eye or both eyes. Other symptoms are weakness or numbness of the arms or legs. Some children experience confusion or extreme lethargy at their attacks. Other possible symptoms including vomiting, fever or seizures.
Diagnosis of pediatric NMO
Diagnosis is usually made by a combination of clinical features, appearance of lesions or “spots” on MRI. Approximately 2/3 of children with NMO can also have an antibody to aquaporin-4 in their blood or spinal fluid, however this antibody may not be present at the onset of the disease, and may be appear up to 2-3 years later. Pediatric NMO differs from MS in the distribution of MRI lesions, as well as the presence of the aquaporin-4 antibody.
Treatment of pediatric NMO
Although there are no FDA approved treatments for adults or children with NMO, children are usually offered immunomodulatory treatments. Attacks are treated with a short course (usually up to a week) of intravenous steroids, or IVIG or plasmapheresis. It is important to prevent new attacks in children with established NMO, and treatment with mycophenolate mofetil, azathioprine or rituximab is usually offered.
Research in pediatric NMO
There is ongoing research to understand the causes of pediatric NMO including genetic associations. As well, studies of better diagnostic and imaging criteria are underway to improve recognition of this condition. Treatment studies and clinical trials of new treatments include children when appropriate.
Management and support for pediatric NMO
There are several centers across the world that have experience in treatment children and adolescents with NMO. Care includes neurological expertise, family support, therapists and affiliation with an educational specialist. Care is often co-managed by a specialist team as well as a patient’s local neurologist or pediatrician.
What is Optic Neuritis?
Optic neuritis is a condition in which swelling and inflammation of the optic nerve leads to decreased vision, including worsening of visual acuity (clarity of vision), color vision, and field of vision.
Who gets Optic Neuritis?
Approximately one-third of children with demyelinating disorders of the central nervous system (CNS) may experience optic neuritis as a first symptom. In most cases, vision will return to almost normal, but subtle changes, including changes in color vision, and contrast vision may occur. These changes may accumulate over time.
Research in Pediatric Optic Neuritis
A recent IPMSSG paper describes current knowledge regarding optic neuritis in children and describes treatment approaches for this condition.
Acute transverse myelitis (ATM)
What is ATM?
Childhood acute transverse myelitis (ATM) occurs when the immune system targets the spinal cord. ATM is a rare but potentially devastating condition with varying possible outcomes. Weakness or paralysis of the legs and/or arms, incontinence and constipation, and loss of sensation usually develop over several hours, and can progress to a severely disabling state.
ATM needs to be distinguished from other rarer spinal cord disorders. ATM may also be an early sign of chronic diseases such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The criteria for diagnosing ATM are generally relevant for children, but some modifications may be necessary in young children.
In ATM, MRI lesions tend to affect a large segment of the spinal cord. MRI lesions of the brain that do not cause symptoms are seen in more than one-third of children with ATM and predict MS or NMO. Children generally have a better outcome than adults, with 50% making a complete recovery within two years.
There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study to date currently open to recruitment.
A recent IPMSSG paper reviews the current knowledge of how ATM develops, its clinical features, the recommended diagnostic workup and management strategies, and suggests future research directions.
Acquired demyelinating syndrome (ADS)
What is ADS?
The first attack of multiple sclerosis (MS) in childhood can appear very different from one child to another. An acute (abrupt) onset of inflammatory demyelination of the central nervous system (CNS) is called acquired demyelinating syndrome (ADS). The demyelination can occur in a single location (unifocal) or in more than one location (polyfocal) in the CNS.
Approximately one third of children with ADS will be diagnosed with MS, typically within 2-4 years after ADS. The diagnosis can sometimes be made immediately based on the 2010 McDonald MS criteria, or later on the basis of additional clinical or MRI evidence of relapsing disease.
The children with ADS who have the highest likelihood of MS are adolescent girls with demyelination in more than one area of the CNS.