Acute disseminated encephalomyelitis and demyelinating disease — formative SAQs

Question 1 (10 marks)

A previously well six-year-old boy presents four days after a viral upper-respiratory illness with fever, drowsiness, and irritability, then over the next twenty-four hours develops a right hemiparesis, slurred speech, and an unsteady gait. His conscious level fluctuates and is not explained by the fever alone. Brain MRI with gadolinium shows diffuse, bilateral, poorly demarcated white-matter lesions with thalamic involvement and patchy enhancement. [1]

(a) Define acute disseminated encephalomyelitis and identify the single clinical feature that distinguishes it from a clinically isolated syndrome such as optic neuritis or transverse myelitis. (3 marks) [1]

(b) Outline the first-line acute treatment, including the drug, the dose, and the duration, and state when and how you would escalate. (4 marks) [4]

(c) Describe the antibody-led workup that resolves the diagnosis and governs the long-term management, naming the three antibody tests and the imaging. (3 marks) [1] [2]

Model answer

Acute disseminated encephalomyelitis is a first, polysymomatic, inflammatory demyelinating event of the central nervous system, defined under the International Pediatric Multiple Sclerosis Study Group criteria by the presence of encephalopathy - an altered conscious level or behaviour not explained by fever alone - alongside multifocal neurological deficits and a diffuse, bilateral white and deep grey matter lesion pattern on MRI. The single distinguishing feature is encephalopathy: its presence defines ADEM, and its absence defines a clinically isolated syndrome, which by definition is non-encephalopathic beyond the irritability expected in a sick child. This child's fluctuating conscious level, dissociated from the fever, establishes the ADEM phenotype. [1]

The first-line acute treatment is high-dose intravenous methylprednisolone at 20 to 30 mg/kg per day to a maximum of 1 g per day, given over three to five days, followed by a short oral prednisolone taper. If the encephalopathy or deficit has not improved after forty-eight to seventy-two hours of corticosteroids - defining steroid-refractory disease - the response is to escalate to intravenous immunoglobulin at a total dose of 2 g/kg (over two to five days) or to plasma exchange (typically five to seven exchanges on alternate days), rather than repeating the steroid course. Plasma exchange is favoured for the most severe attacks because it removes the pathogenic antibody and complement directly. [4]

The workup is run in parallel with the acute treatment. An urgent brain and spinal MRI with gadadolium assesses the lesion pattern and dissemination in space; the serum is sent for myelin-oligodendrocyte-glycoprotein IgG and aquaporin-4 IgG by a live cell-based assay (the assay matters, because fixed-cell ELISA assays produce false positives); and a lumbar puncture provides cerebrospinal-fluid oligoclonal bands on a paired serum sample, which, if unique to the CSF, support paediatric multiple sclerosis and can substitute for dissemination in time under the 2017 McDonald criteria. The antibody triad - MOG-IgG, AQP4-IgG, and oligoclonal bands - is what resolves the provisional ADEM phenotype into a confirmed diagnosis and governs the long-term treatment. [1] [2]

Question 2 (10 marks)

A thirteen-year-old girl of South Asian ancestry presents with five days of intractable hiccups, nausea, and vomiting, followed by pain and complete visual loss in both eyes and a flaccid paraplegia with urinary retention. Spinal MRI shows a longitudinally extensive transverse myelitis spanning six vertebral segments. Her serum aquaporin-4 IgG is positive and myelin-oligodendrocyte-glycoprotein IgG is negative. [3]

(a) Name the syndrome that explains the hiccups, nausea, and vomiting, state its lesion location, and give the diagnosis. (3 marks) [3]

(b) Explain why a multiple-sclerosis disease-modifying therapy must not be started in this patient, and name the class of maintenance therapy that is appropriate. (4 marks) [3] [6]

(c) Describe the acute attack management for the bilateral optic neuritis and myelitis, including the role of plasma exchange. (3 marks) [4] [6]

Model answer

The hiccups, nausea, and vomiting constitute the area-postrema syndrome, which reflects a lesion at the area postrema on the floor of the fourth ventricle and is a hallmark core clinical characteristic of AQP4-IgG-positive neuromyelitis optica spectrum disorder. Combined with severe bilateral optic neuritis and a longitudinally extensive transverse myelitis spanning three or more vertebral segments, in a patient of non-European ancestry with coexisting autoimmunity, this fulfills the IPND 2015 criteria for NMOSD (AQP4-IgG plus one or more core clinical characteristics and a compatible MRI). The diagnosis is neuromyelitis optica spectrum disorder. [3]

A multiple-sclerosis disease-modifying therapy must not be started because NMOSD is an antibody-complement astrocytopathy (aquaporin-4 IgG targets the astrocyte water channel), biologically distinct from the T-cell- and B-cell-driven disease that the multiple-sclerosis drugs target, and several multiple-sclerosis drugs - including interferon-beta, natalizumab in some series, and fingolimod - have been associated with worsening relapse frequency and severity in AQP4-IgG-positive disease. The appropriate maintenance therapy is a NMOSD-specific drug: rituximab or another anti-CD20 agent, mycophenolate mofetil, azathioprine, satralizumab (an interleukin-6 receptor blocker), or a complement blocker (eculizumab, ravulizumab), chosen by attack severity, coexisting autoimmunity, and access. The biological mismatch is the reason the antibody status is awaited before any long-term drug. [3] [6]

The acute attack is treated identically to any demyelinating event with high-dose intravenous methylprednisolone 20 to 30 mg/kg per day to a maximum of 1 g per day for three to five days, and because this is a severe AQP4-IgG-positive attack, early plasma exchange - five to seven exchanges of one to one-and-a-half plasma volumes on alternate days - is favoured to remove the pathogenic antibody and complement directly and to improve the attack outcome. Intravenous immunoglobulin is an alternative for steroid-refractory disease. Rehabilitation for vision and mobility, bladder and bowel management, and a structured transition plan are begun early alongside the medical therapy. [4] [6]