Myelin Oligodendrocyte Glycoprotein–Associated Disorders
Introduction to MOG-AD in Children
Myelin Oligodendrocyte Glycoprotein–Associated Disorders (MOG-AD) represent a spectrum of inflammatory demyelinating conditions of the central nervous system (CNS) characterized by the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG). These disorders have gained significant recognition in recent years, particularly in pediatric populations.
MOG-AD encompasses various clinical phenotypes, including:
- Acute Disseminated Encephalomyelitis (ADEM)
- Optic Neuritis (ON)
- Transverse Myelitis (TM)
- Neuromyelitis Optica Spectrum Disorders (NMOSD)-like presentations
- Encephalitis
Understanding MOG-AD is crucial for pediatric neurologists and ophthalmologists, as it represents a distinct entity from other demyelinating disorders such as Multiple Sclerosis (MS) and Aquaporin-4 antibody-positive NMOSD, with implications for treatment and prognosis.
Pathophysiology of MOG-AD
The pathophysiology of MOG-AD involves an autoimmune response targeting the myelin oligodendrocyte glycoprotein:
- MOG Protein: A glycoprotein expressed on the surface of myelin sheaths and oligodendrocytes in the CNS.
- Antibody Production: B cells produce antibodies against MOG, leading to an autoimmune response.
- Blood-Brain Barrier: These antibodies can cross the blood-brain barrier, especially in children where the barrier may be more permeable.
- Complement Activation: MOG antibodies can activate the complement system, leading to inflammation and demyelination.
- T-cell Involvement: T cells may also play a role in the inflammatory process, though their exact contribution is still under investigation.
The pathology of MOG-AD differs from that of MS and AQP4-positive NMOSD:
- Less astrocyte damage compared to AQP4-positive NMOSD
- More preservation of axons compared to MS
- Predominant involvement of the optic nerves and spinal cord, though brain lesions can occur, especially in children
The exact trigger for MOG antibody production remains unclear, but genetic predisposition and environmental factors (e.g., preceding infections) may play a role.
Clinical Presentation
The clinical presentation of MOG-AD in children can be diverse and age-dependent:
- Optic Neuritis (ON):
- Often bilateral (more common in children than adults)
- Can be recurrent
- May present with severe vision loss
- Optic disc edema is common
- Acute Disseminated Encephalomyelitis (ADEM):
- More common in younger children
- Encephalopathy (altered consciousness, behavioral changes)
- Multifocal neurological deficits
- Often preceded by a viral illness
- Transverse Myelitis (TM):
- Can be complete or partial
- Motor weakness, sensory disturbances
- Bladder and bowel dysfunction
- NMOSD-like Presentation:
- Combination of ON and TM
- Area postrema syndrome (intractable hiccups, nausea, vomiting)
- Encephalitis:
- Seizures
- Cognitive impairment
- Behavioral changes
Key features of MOG-AD in children include:
- Higher likelihood of polyphasic or recurrent course compared to monophasic ADEM
- Potential for severe residual visual impairment after ON
- Age-dependent phenotypes (e.g., ADEM more common in younger children, ON/TM more common in older children and adolescents)
Diagnosis
Diagnosing MOG-AD in children requires a combination of clinical, radiological, and serological assessments:
- Clinical Evaluation:
- Detailed neurological examination
- Ophthalmological assessment (including visual acuity, color vision, visual fields)
- Evaluation of other systemic symptoms
- Neuroimaging:
- MRI of brain, spine, and orbits with and without contrast
- Typical findings: Large, poorly demarcated lesions; deep gray matter involvement in ADEM; longitudinally extensive transverse myelitis (LETM)
- Optic nerve involvement often bilateral with anterior predominance and perineural enhancement
- Serology:
- Detection of serum MOG-IgG antibodies using cell-based assays (CBAs)
- Negative AQP4-IgG antibodies
- Cerebrospinal Fluid (CSF) Analysis:
- May show pleocytosis and elevated protein
- Oligoclonal bands typically absent (in contrast to MS)
- Optical Coherence Tomography (OCT):
- Can show retinal nerve fiber layer thinning in ON
- Visual Evoked Potentials (VEP):
- May show delayed latencies in ON
Diagnostic Challenges:
- Differentiation from other demyelinating disorders (MS, AQP4-positive NMOSD)
- Transient MOG-IgG positivity in some children, especially following ADEM
- Need for repeat testing in seronegative cases with high clinical suspicion
A combination of typical clinical presentations, characteristic MRI findings, and positive MOG-IgG antibodies is required for a definitive diagnosis of MOG-AD.
Treatment
The treatment of MOG-AD in children focuses on acute management of relapses and long-term prevention of recurrences:
- Acute Treatment:
- High-dose intravenous methylprednisolone (20-30 mg/kg/day, max 1g/day) for 3-5 days
- Followed by oral prednisone taper over 2-3 months
- Intravenous Immunoglobulin (IVIG) for steroid-resistant cases
- Plasma exchange for severe, refractory cases
- Maintenance Therapy:
- Decision based on disease course (monophasic vs. relapsing)
- Options include:
- Monthly IVIG
- Rituximab
- Mycophenolate mofetil
- Azathioprine
- Prolonged steroid taper may be necessary in some cases
- Symptomatic Management:
- Pain management
- Spasticity treatment
- Bladder and bowel management
- Visual rehabilitation
Treatment Considerations:
- Early initiation of treatment is crucial for better outcomes
- Treatment duration is individualized based on clinical course and antibody status
- Regular monitoring of MOG-IgG titers can guide treatment decisions
- Avoid MS-specific therapies (e.g., interferon-beta, natalizumab) as they may be ineffective or potentially harmful in MOG-AD
The treatment approach should be tailored to the individual child, considering the severity of the disease, frequency of relapses, and potential side effects of long-term immunosuppression.
Prognosis
The prognosis of MOG-AD in children is generally more favorable compared to other demyelinating disorders, but can vary significantly:
- Disease Course:
- Monophasic course: More common in younger children with ADEM-like presentation
- Relapsing course: More frequent in older children and those with ON or NMOSD-like phenotypes
- Recovery from Acute Episodes:
- Often good recovery, especially with prompt treatment
- Visual outcomes can be variable, with potential for residual deficits after ON
- Long-term Outcomes:
- Generally better than AQP4-positive NMOSD
- Lower disability accumulation compared to MS
- Risk of cognitive impairment, especially in those with brain involvement
- Factors Influencing Prognosis:
- Age at onset (younger age often associated with monophasic course)
- Initial phenotype (ADEM-like presentations often have better outcomes)
- Time to treatment initiation
- Frequency and severity of relapses
- Antibody Status:
- Persistent MOG-IgG positivity associated with higher relapse risk
- Antibody titers may fluctuate or become negative over time
Long-term Monitoring:
- Regular neurological and ophthalmological assessments
- Periodic MRI scans to monitor disease activity
- Cognitive evaluations, especially in children with brain involvement
- MOG-IgG antibody monitoring to guide treatment decisions
While the overall prognosis is favorable, some children may experience significant residual deficits, particularly visual impairment following severe or recurrent optic neuritis. Early diagnosis, prompt treatment, and appropriate long-term management are key to optimizing outcomes in pediatric MOG-AD.
Myelin Oligodendrocyte Glycoprotein–Associated Disorders
- What is Myelin Oligodendrocyte Glycoprotein (MOG)?
A protein found on the surface of myelin sheaths in the central nervous system - What are MOG antibodies?
Autoantibodies that target MOG, leading to demyelination - Which age group is most commonly affected by MOG-associated disorders?
Children and young adults - What is the most common clinical presentation of MOG-associated disorders in children?
Acute disseminated encephalomyelitis (ADEM) - Which test is used to diagnose MOG-associated disorders?
Serum MOG-IgG antibody test - What is the characteristic MRI finding in MOG-associated disorders?
Bilateral, large, ill-defined white matter lesions - How do MOG-associated disorders differ from Multiple Sclerosis (MS)?
MOG disorders typically have a monophasic or relapsing course, while MS is usually progressive - What is the most common ocular manifestation of MOG-associated disorders?
Optic neuritis - Which type of optic neuritis is more common in MOG-associated disorders?
Bilateral optic neuritis - What is the typical cerebrospinal fluid finding in MOG-associated disorders?
Pleocytosis with predominant lymphocytes - How do MOG-associated disorders differ from Neuromyelitis Optica Spectrum Disorders (NMOSD)?
MOG disorders are AQP4 antibody negative and have a better prognosis - What is the first-line treatment for acute attacks in MOG-associated disorders?
High-dose intravenous methylprednisolone - Which immunosuppressive medication is commonly used for long-term management of MOG-associated disorders?
Mycophenolate mofetil - What is the role of plasma exchange in treating MOG-associated disorders?
Used in severe cases unresponsive to steroid treatment - Which MOG-associated disorder presents with seizures and encephalopathy?
MOG antibody-associated encephalitis - What is the prognosis for children with MOG-associated disorders?
Generally good, with many patients having a monophasic course - How often should MOG antibody levels be monitored in patients with MOG-associated disorders?
Every 6-12 months or during relapses - What is the typical duration of immunosuppressive treatment in MOG-associated disorders?
At least 2 years after the last relapse - Which cranial nerve is most commonly affected in MOG-associated disorders?
Optic nerve (cranial nerve II) - What is the role of rituximab in treating MOG-associated disorders?
Used in cases refractory to first-line immunosuppressive treatments - How do MOG-associated disorders affect the spinal cord?
Can cause transverse myelitis, often with longitudinally extensive lesions - What is the typical age of onset for MOG-associated disorders in children?
Between 3-10 years old - Which environmental factor has been associated with the onset of MOG-associated disorders?
Preceding viral infections - What is the role of intravenous immunoglobulin (IVIG) in treating MOG-associated disorders?
Used as maintenance therapy or for acute relapses - How do MOG-associated disorders affect cognitive function in children?
Cognitive impairment is generally less severe compared to other demyelinating disorders - What is the recommended follow-up imaging protocol for patients with MOG-associated disorders?
MRI of brain and spine every 6-12 months or when new symptoms occur - Which MOG-associated disorder presents with area postrema syndrome?
MOG antibody-associated brainstem encephalitis - What is the role of B-cell depletion therapy in MOG-associated disorders?
Used in cases with frequent relapses or severe disease course - How do MOG-associated disorders affect the optic chiasm?
Can cause chiasmal involvement leading to bitemporal hemianopia - What is the typical cerebrospinal fluid oligoclonal band finding in MOG-associated disorders?
Usually negative, in contrast to Multiple Sclerosis
