Contrasting diagnostic challenges of headache before and after acute disseminated encephalomyelitis in children: Two case reports and review of literature

Table 1 Differential diagnosis considered during the initial evaluation of case 1

Diagnostic possibility	Findings supporting	Findings non-supportive
Primary migraine	Maternal migraine history	New continuous headache, fever, confusion, pyramidal signs, MRI abnormalities
Sinusitis	Allergic rhinitis, frontal pain	Neurological deterioration and MRI findings
Viral encephalitis	Fever, vomiting, CSF lymphocytic pleocytosis and elevated protein	Negative multiplex CSF PCR panel for neurotropic viruses, characteristic ADEM MRI pattern
ADEM	Encephalopathy, multifocal signs, characteristic MRI	-
MS	Demyelinating lesions	Large poorly marginated lesions, relative periventricular sparing, monophasic pediatric clinical phenotype
Serum MOGAD	ADEM phenotype	Serum MOG-IgG negative by cell-based assay
Raised intracranial pressure/intracranial structural disease	Severe persistent headache, vomiting, and transient visual blurring could raise concern for increased intracranial pressure or an intracranial structural lesion	Normal fundoscopic examination without papilledema; normal CSF opening pressure (140 mm H2O); brain MRI demonstrated multifocal bilateral white-matter lesions consistent with ADEM rather than a focal mass lesion or structural abnormality

MRI: Magnetic resonance imaging; CSF: Cerebrospinal fluid; PCR: Polymerase chain reaction; ADEM: Acute disseminated encephalomyelitis; MS: Multiple sclerosis; MOGAD: Myelin oligodendrocyte glycoprotein antibody-associated disease; MOG-IgG: Myelin oligodendrocyte glycoprotein immunoglobulin G.

Table 2 Key laboratory and diagnostic investigations

Investigation (collection time point)	Reference range	Case 1 (day +3)	Case 2 (initial acute presentation)/case 2 (3-month readmission)
CSF opening pressure	60-200 mm H2O	Normal (140 mm H2O)	Initial: Normal (130 mm H2O)/3-month: Normal (125 mm H2O)
CSF cells	0-5 lymphocytes/μL	50/μL (lymphocytic predominance)	Initial: 2 lymphocytes/μL/3-month: 1 lymphocyte/μL
CSF protein	15-45 mg/dL	Elevated (75 mg/dL)	Initial: Normal (41 mg/dL)/3-month: Normal (38 mg/dL)
CSF glucose	50-80 mg/dL (or ≥ 60% of serum)	Normal (55 mg/dL)	Initial: Normal (63 mg/dL)/3-month: Normal (60 mg/dL)
Serum glucose	70-110 mg/dL	89 mg/dL	92 mg/dL
OCB	Negative	Negative (CSF and serum)	Not detected
Serum MOG-IgG (pre-treatment)	Negative (< 1:16 titer)	Negative (by live cell-based assay)	Negative (by live cell-based assay)
Serum AQP4-IgG (pre-treatment)	Negative (< 1:16 titer)	Negative (by live cell-based assay)	Negative (by live cell-based assay)
MRI brain	Normal	ADEM pattern (multifocal white matter lesions, no restricted diffusion, no contrast enhancement)	ADEM pattern (bilateral confluent white matter lesions, no restricted diffusion, no contrast enhancement)
MRI spine	Normal	Normal	Normal
EEG	Normal organization	Diffuse and focal background slowing	Not tested

CSF: Cerebrospinal fluid; OCB: Oligoclonal bands; MOG-IgG: Myelin oligodendrocyte glycoprotein immunoglobulin G; AQP4-IgG: Aquaporin-4 immunoglobulin G; MRI: Magnetic resonance imaging; ADEM: Acute disseminated encephalomyelitis; EEG: Electroencephalography.