25.1 Fulminant Demyelinating Diseases (03.P)
Key Takeaways
- Adult acute demyelinating attacks are treated with intravenous methylprednisolone 1 g daily for 3–5 days; escalate to plasma exchange for severe or steroid-refractory NMOSD myelitis or optic neuritis rather than waiting for a slow oral taper.
- AQP4-IgG NMOSD is an astrocytopathy whose core ICU syndromes are severe optic neuritis, longitudinally extensive transverse myelitis, and area postrema intractable nausea, vomiting, or hiccups; interferon, natalizumab, and fingolimod can worsen NMOSD and are not rescue therapy.
- ADEM is typically monophasic and encephalopathy-predominant with multifocal MRI lesions; Marburg-type fulminant MS produces tumefactive, confluent lesions with herniation risk and may need biopsy to exclude abscess or glioma.
- Distinguish bacterial abscess, HSV encephalitis, and PML from inflammatory relapse before committing to days of high-dose steroids when the picture is mixed; cover infection in parallel if you cannot wait.
- Longitudinally extensive myelitis at C3–C5 can cause diaphragmatic failure while limb strength is still present; serial vital capacity and inspiratory force should trigger a controlled intubation.
Why fulminant demyelination belongs in the ICU
Fulminant demyelinating disease can take a walking patient to ventilator-dependent quadriplegia, blindness, or herniation in hours to a few days. The ABPN Neurocritical Care Certification Content Specifications (posted December 23, 2021) list this cluster as topic 03.P. The neurocritical care job is pattern recognition across acute disseminated encephalomyelitis (ADEM), Marburg-type (fulminant) multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD); time-critical treatment of optic neuritis (ON), transverse myelitis (TM), and area postrema attacks; distinguishing infection before high-dose steroids when possible; and anticipating respiratory failure from high cervical cord lesions.
This OpenExamPrep chapter teaches those ICU decisions. It does not claim official endorsement by ABIM, ABPN, or any specialty society.
Shared attack care, different biology
These diseases share a treatment skeleton: confirm a central nervous system inflammatory attack, exclude the dangerous mimics, give high-dose intravenous methylprednisolone (IVMP) (typically 1 g daily for 3–5 days in adults, with gastric protection and glucose control), and escalate to plasma exchange (PLEX) when the attack is severe or steroid-refractory. They do not share the same antibody, MRI signature, relapse biology, or maintenance drugs. Using an MS disease-modifying drug in AQP4-IgG NMOSD can worsen attacks. That distinction is an examination favorite.
PLEX for a severe attack is commonly 5–7 exchanges of about 1–1.5 plasma volumes. Start it when vision is collapsing, the patient is becoming paraplegic, or there is no meaningful improvement after the steroid pulse—not after a leisurely two-week oral taper. For previously PLEX-responsive NMOSD, or for severe LETM, many expert groups (including the Neuromyelitis Optica Study Group, NEMOS) support early or simultaneous PLEX with steroids rather than a failed-steroid-only sequence.
ADEM
ADEM is typically a monophasic, post-infectious or, less often, post-vaccination inflammatory attack. Encephalopathy—behavioral change, irritability, or impaired consciousness—is required in pediatric diagnostic frameworks and is the clinical clue that this is not isolated ON or TM. MRI shows multifocal, often large, poorly marginated T2/FLAIR lesions in white matter, with frequent basal ganglia or thalamic involvement. Enhancement, when present, may be incomplete or open-ring. Cerebrospinal fluid (CSF) can show a mild lymphocytic pleocytosis; unmatched oligoclonal bands are less often persistently positive than in MS.
Treat with IVMP. If the patient does not improve, intravenous immunoglobulin (IVIG) (often 2 g/kg over 2–5 days) or PLEX is used. Biopsy is reserved for mass-like lesions that look like abscess, tumor, or Marburg disease. A second inflammatory event should trigger MOG-IgG and AQP4-IgG testing rather than an automatic lifelong MS label. Multiphasic ADEM and MOGAD overlap; the ICU still treats the attack in front of you.
Fulminant MS and the Marburg variant
Marburg-type MS is a rare, fulminant demyelinating illness with large, confluent, often tumefactive lesions, rapid disability, and a real risk of herniation. Ring enhancement and mass effect mimic glioma and pyogenic abscess. When infection and tumor cannot be excluded, cover with antimicrobials (including acyclovir if herpes simplex virus encephalitis is plausible), obtain a biopsy if the patient is stable enough, and still treat cerebral edema.
ICU care is mass-effect care: head of bed, sodium and osmolarity targets, hypertonic saline or mannitol, brief hyperventilation only as a bridge to osmotherapy or decompression, and neurosurgical decompression in selected herniating patients. Immunotherapy is high-dose steroids plus early PLEX; cyclophosphamide is sometimes added in true Marburg disease. This is not the setting to start interferon-beta or natalizumab as rescue therapy.
NMOSD: AQP4 astrocytopathy
NMOSD associated with aquaporin-4 immunoglobulin G (AQP4-IgG) is an astrocytopathy, not a mild MS cousin. Disability accumulates with attacks, so each relapse is an emergency. Core clinical features in the International Panel for NMO Diagnosis (IPND) 2015 framework include:
- Severe ON, often longitudinally extensive on orbital MRI, with a high risk of residual blindness
- Longitudinally extensive transverse myelitis (LETM), typically three or more vertebral segments, often central cord, and frequently cervicomedullary
- Area postrema syndrome: intractable nausea, vomiting, or hiccups from a dorsal medullary lesion—easy to miss as gastritis
- Acute brainstem, diencephalic (narcolepsy, hyponatremia), and symptomatic cerebral syndromes
Serum cell-based AQP4-IgG is the diagnostic anchor. CSF may show neutrophils and often lacks unmatched oligoclonal bands. Brain MRI can be normal or show lesions around the third and fourth ventricles, area postrema, and hypothalamus rather than typical MS periventricular ovoids.
Acute treatment: IVMP 1 g daily for 3–5 days. PLEX for steroid-refractory attacks, and increasingly early PLEX for severe myelitis or ON. IVIG is a fallback when apheresis is contraindicated. After the attack, start attack-prevention immunotherapy used in practice (rituximab, inebilizumab, satralizumab, complement inhibitors such as eculizumab or ravulizumab, or older agents such as azathioprine or mycophenolate). Do not use interferon-beta, natalizumab, fingolimod, or alemtuzumab as if this were MS.
MOGAD
MOGAD is an oligodendrocytopathy diagnosed with MOG-IgG on a cell-based assay (live cell-based testing is preferred when available). Children often present with ADEM; adults often present with ON (frequently bilateral, with optic-disc edema) or TM that may be long or short. Recovery is often better than in AQP4 NMOSD, but early relapse during a steroid taper is classic. Acute treatment is IVMP; many clinicians add a slower oral taper and use IVIG for incomplete response or pediatric ADEM-MOGAD. PLEX is used for severe, steroid-refractory disability. The examination job in the ICU is the attack, not maintenance trivia.
Distinguish infection before steroids when possible
High-dose steroids worsen untreated bacterial abscess, fungal disease, and some parasitic infections, and they do not treat HSV. Before you commit to days of IVMP:
- Fever, neutrophilic CSF, HIV risk, endocarditis, and a single ring-enhancing lesion favor infection or tumor.
- Start empiric acyclovir when HSV encephalitis is in the differential (temporal T2/FLAIR, periodic EEG, hemorrhagic CSF) and stop it only when polymerase chain reaction is negative on an adequate sample.
- Progressive multifocal leukoencephalopathy (PML) is a JC-virus infection, not an inflammatory relapse, in natalizumab-treated MS; more steroids without a PML strategy can harm.
- When the picture is still mixed, cover infection and treat inflammation in parallel, then de-escalate with PCR, cultures, and antibodies.
Delaying all immunotherapy for a week of cultures in a patient who is going blind from AQP4 ON is the opposite error. The stem will tell you whether fever, ring enhancement, and risk factors are present.
High cervical cord and the airway
LETM and Marburg-like cord lesions at C3–C5 hit the phrenic motor pool. Patients may still wiggle their toes while the diaphragm fails. Serial forced vital capacity (FVC) and negative inspiratory force (NIF), a weak cough, orthopnea, and rising carbon dioxide should move the patient to a controlled intubation. Neurogenic shock (hypotension with relative bradycardia) can accompany high cervical involvement. Do not attribute every desaturation to MS fatigue.
| Feature | ADEM | Marburg / fulminant MS | AQP4 NMOSD | MOGAD |
|---|---|---|---|---|
| Typical host | Child or young adult after infection | Rapidly disabling adult | Adult woman; severe, attack-driven disability | Child (ADEM) or adult (ON/TM) |
| Signature | Encephalopathy plus multifocal MRI | Tumefactive, confluent, herniation risk | LETM, severe ON, area postrema | Bilateral ON with disc edema; steroid-taper relapse |
| Antibody | Usually none | None (MS biology) | AQP4-IgG (cell-based assay) | MOG-IgG (cell-based assay) |
| Acute ICU therapy | IVMP; IVIG or PLEX if refractory | IVMP plus early PLEX; edema care | IVMP; PLEX early if severe | IVMP ± IVIG; PLEX if severe |
| Maintenance pitfall | Over-calling MS after one event | None specific | MS drugs can worsen NMOSD | Over-rapid steroid taper |
Examination traps
- Treating area postrema vomiting as gastroenteritis for a week.
- Starting natalizumab for aggressive MS that is actually AQP4 NMOSD.
- Giving days of IVMP for a ring-enhancing mass without considering abscess or lymphoma.
- Missing impending respiratory failure from a C3–C4 lesion because limb strength is not zero.
- Ruling out ADEM because the adult patient is not a child; adults get ADEM, just less often.
A 34-year-old woman has three days of intractable hiccups and vomiting. MRI shows a dorsal medullary T2 lesion. Serum AQP4-IgG is pending. Limb strength is normal. Which acute plan is most appropriate?
A febrile patient with a single ring-enhancing hemispheric mass is being considered for 1 g of methylprednisolone daily for suspected Marburg-type demyelination. Which statement is most accurate?
A patient with AQP4-IgG-positive longitudinally extensive myelitis from C2 to C6 has preserved leg withdrawal but a falling forced vital capacity. Which respiratory statement is correct?
Which comparison of ADEM, MOGAD, and AQP4 NMOSD is most accurate for ICU attack care?