Overview
Definition:
Acute Demyelinating Encephalomyelitis (ADEM) is a rare, monophasic, immune-mediated inflammatory disease characterized by widespread demyelination in the central nervous system (CNS), typically occurring after an infection or vaccination
Multiple Sclerosis (MS) is a chronic, relapsing-remitting or progressive autoimmune disease involving immune-mediated demyelination and axonal damage in the CNS, leading to neurological deficits
In pediatrics, differentiating these two entities is crucial due to distinct management and prognostic implications.
Epidemiology:
ADEM is more common in children than adults, with a peak incidence between ages 5-10 years
It accounts for a significant proportion of acute CNS demyelinating events in children
Pediatric MS (PMS) is less common than ADEM, with onset typically in adolescence, though early-onset MS can occur
While ADEM is often monophasic, PMS is characterized by recurrent episodes.
Clinical Significance:
Accurate differentiation between ADEM and PMS is vital for guiding treatment strategies, predicting long-term outcomes, and managing parental expectations
Misdiagnosis can lead to inappropriate therapies, impacting neurological recovery and increasing the risk of future demyelinating events
Understanding the nuances is critical for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
ADEM: Abrupt onset of multifocal neurological deficits, often following a prodromal febrile illness (viral or bacterial) or vaccination (1-2 weeks prior)
Common symptoms include encephalopathy (lethargy, confusion, coma), focal neurological deficits (hemiparesis, cranial nerve palsies, ataxia), and seizures
MS: Relapsing-remitting pattern is most common in children, with episodes of new or worsening neurological symptoms lasting days to weeks, followed by partial or complete recovery
Common symptoms include optic neuritis (vision loss, pain), sensory disturbances (numbness, tingling), motor weakness, ataxia, and bowel/bladder dysfunction
Encephalopathy is rare in typical MS relapses.
Signs:
ADEM: Altered mental status, fever, nuchal rigidity, focal neurological deficits corresponding to CNS lesions (e.g., hemiparesis, cranial nerve deficits), hyperreflexia, Babinski sign
MS: Visual impairment (optic disc pallor/swelling), focal neurological deficits, nystagmus, spasticity, hyperreflexia, sensory loss
Encephalopathy is typically absent.
Diagnostic Criteria:
No universally agreed-upon diagnostic criteria exist for ADEM, but it is generally diagnosed based on clinical presentation, characteristic MRI findings, exclusion of other causes, and sometimes the presence of a preceding trigger
For MS, the 2017 McDonald criteria are widely used, adapted for pediatric populations
Key for pediatric MS includes dissemination in time and space (DIS and DIT) evidenced by MRI lesions in different locations and at different times, with objective neurological evidence of CNS lesions.
Diagnostic Approach
History Taking:
Crucial to elicit a history of recent infection (e.g., upper respiratory, gastroenteritis) or vaccination (typically 1-2 weeks prior to ADEM onset)
Note the rapidity of symptom onset and presence of encephalopathy
For MS, focus on recurrent neurological episodes, their pattern, and duration
Ask about prior episodes, visual disturbances, sensory changes, and motor difficulties
Family history of autoimmune diseases or neurological disorders is relevant.
Physical Examination:
Comprehensive neurological examination, including assessment of mental status, cranial nerves, motor strength, sensation, coordination, reflexes, and gait
Look for signs of meningeal irritation in ADEM
Fundoscopy to assess for optic nerve involvement in suspected MS
Thorough assessment of vital signs, particularly temperature, to rule out infection.
Investigations:
MRI Brain with contrast is the cornerstone
ADEM: Typically shows unilateral or bilateral, large, ovoid, ill-defined lesions, predominantly in the white matter, often involving deep gray matter structures (thalami, basal ganglia)
Lesions are usually T2/FLAIR hyperintense and show patchy post-contrast enhancement, reflecting active inflammation
MS: Demonstrates lesions in characteristic periventricular, juxtacortical, infratentorial, and spinal cord locations
Characteristic features include T2/FLAIR hyperintense lesions, infratentorial lesions, periventricular lesions with ovoid shape and long axis perpendicular to the ventricles (Dawson's fingers), and contrast-enhancing lesions indicating active inflammation
Lumbar Puncture: Cerebrospinal fluid (CSF) analysis in ADEM may show mild pleocytosis and elevated protein, but is often normal
Oligoclonal bands are typically absent
In MS, CSF may show pleocytosis, elevated protein, and importantly, presence of oligoclonal bands and/or elevated IgG index
Laboratory tests: Complete blood count (CBC) with differential, electrolytes, renal and liver function tests, ESR, CRP to rule out systemic inflammation or infection
Autoimmune markers (ANA, anti-dsDNA, ANCA) may be considered to rule out connective tissue diseases
Infectious workup (serology for common viruses) may be useful
Evoked potentials (visual, brainstem auditory, somatosensory) can demonstrate subclinical lesions in MS.
Differential Diagnosis:
Other causes of acute neurological dysfunction in children should be excluded
These include acute encephalitis (infectious), stroke, metabolic encephalopathies, seizures, hypoxic-ischemic injury, brain tumors, paraneoplastic syndromes, and neuromyelitis optica spectrum disorder (NMOSD)
Differentiating ADEM from MS relies on the monophasic nature and encephalopathy of ADEM vs
the relapsing course and multifocal lesions in distinct locations typical of MS
NMOSD typically involves optic nerves and spinal cord with characteristic MRI findings (e.g., large, longitudinally extensive spinal cord lesions)
Autoimmune encephalitis (e.g., anti-NMDAR encephalitis) presents with severe encephalopathy and psychiatric symptoms and has specific antibody markers.
Management
Initial Management:
Supportive care is paramount for both conditions
This includes airway management, fluid and electrolyte balance, seizure control, and management of fever
For ADEM, prompt initiation of immunomodulatory therapy is crucial
For suspected MS, management is guided by the presence of relapses or disease progression
Admission to an intensive care unit may be required for severely affected patients with ADEM.
Medical Management:
ADEM: High-dose intravenous methylprednisolone (IVMP) is the first-line treatment, typically 10-30 mg/kg/day for 3-5 days, followed by a tapering course of oral corticosteroids
Intravenous immunoglobulin (IVIG) (2 g/kg total dose over 2-5 days) is often used as an adjunctive therapy
Plasmapheresis may be considered in severe or refractory cases
MS: For relapses in pediatric MS, IVMP (10-30 mg/kg/day) is used for 3-5 days, followed by oral corticosteroid tapering
Disease-modifying therapies (DMTs) are used for patients with frequent relapses or significant disability accumulation
Options in pediatrics include interferon-beta, glatiramer acetate, natalizumab, fingolimod, and rituximab, with the choice depending on disease severity, age, and patient factors
Education on adherence and monitoring for side effects is essential.
Surgical Management:
Surgical intervention is generally not indicated for ADEM or MS unless complications arise, such as hydrocephalus requiring shunting or intractable status epilepticus requiring consideration of specific interventions.
Supportive Care:
Ongoing monitoring of neurological status, vital signs, and fluid balance
Physical therapy, occupational therapy, and speech therapy are essential for rehabilitation and managing functional deficits
Psychological support for patients and families is critical, especially given the chronic nature of MS and the severity of ADEM.
Complications
Early Complications:
ADEM: Seizures, status epilepticus, cerebral edema, hydrocephalus, respiratory failure, secondary infections, electrolyte imbalances, disseminated intravascular coagulation (DIC)
MS: Urinary tract infections, pressure ulcers, pneumonia, dysphagia, emotional lability, fatigue, heat intolerance.
Late Complications:
ADEM: Residual neurological deficits, cognitive impairment, behavioral changes, epilepsy
MS: Permanent neurological disability, depression, chronic pain, visual impairment, spasticity, bladder and bowel dysfunction, disease progression leading to secondary progressive MS in some cases.
Prevention Strategies:
For ADEM, while direct prevention is difficult, prompt diagnosis and aggressive immunomodulatory treatment can mitigate severity and reduce long-term sequelae
For MS, adherence to prescribed DMTs and regular medical follow-up is key to preventing relapses and disease progression
Proactive management of common complications like UTIs and pressure sores is crucial.
Prognosis
Factors Affecting Prognosis:
ADEM: Factors influencing prognosis include the severity of initial presentation (especially degree of encephalopathy and neurological deficits), response to treatment, and extent of brain lesions
While many children recover fully, some may have residual deficits
MS: Prognosis varies widely
Factors include age at onset (earlier onset may be associated with more relapses initially but potentially better long-term recovery), disease course (relapsing-remitting vs
progressive), lesion load, and response to DMTs
Early and effective treatment can significantly improve long-term outcomes and reduce disability accumulation.
Outcomes:
ADEM: Most children experience significant recovery, often within weeks to months
However, a subset may have permanent neurological sequelae
MS: Pediatric MS often presents with a higher relapse rate compared to adult-onset MS but may have a better prognosis for recovery from individual relapses
Long-term disability accumulation is a concern, and continuous monitoring and treatment are necessary
Many children with pediatric MS can achieve good functional status with appropriate management.
Follow Up:
Regular neurological follow-up is essential for both ADEM and MS
For ADEM, follow-up focuses on monitoring for recovery and managing any residual deficits
For MS, long-term follow-up is critical to monitor disease activity (relapses and new MRI lesions), assess disability progression, adjust DMTs as needed, and manage complications
Annual neurological evaluations, including MRI scans, are typically recommended
Psychiatric and rehabilitation services should be integrated into long-term care plans.
Key Points
Exam Focus:
Distinguishing monophasic ADEM with encephalopathy from relapsing MS without encephalopathy is paramount
MRI findings are key: ADEM often shows large, ill-defined lesions involving deep gray matter
MS shows lesions in typical white matter locations (periventricular, juxtacortical) with characteristic patterns
CSF oligoclonal bands are typically absent in ADEM and present in MS
High-dose steroids are first-line for both acute attacks, but DMTs are crucial for managing MS long-term.
Clinical Pearls:
Always consider a preceding infection or vaccination in ADEM
Encephalopathy is a red flag for ADEM over MS
In MS, look for the "dissemination in time and space" on MRI
Monitor for complications aggressively, especially in severe ADEM
For pediatric MS, early initiation of DMTs can significantly alter the disease course.
Common Mistakes:
Misdiagnosing ADEM as an infectious encephalitis without considering demyelination
Failing to recognize the monophasic nature of ADEM and inappropriately treating it with long-term MS therapies
Underestimating the significance of encephalopathy in the differential diagnosis of demyelinating disorders
Delaying immunomodulatory treatment in ADEM, impacting recovery
Inadequate follow-up and monitoring for disease activity in pediatric MS, leading to disability progression.