Unravelling demyelination: A case of antibody-negative ADEM with NMOSD overlap and peripheral involvement
Year: 2025
Type: article
Abstract: To the Editor, Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder that generally affects children and young adults. Although ADEM typically follows an infection or vaccination, cases lacking classical serological markers present substantial diagnostic challenges. We report a case of severe, seronegative ADEM with extensive central nervous system involvement, underscoring the need for advanced imaging and prompt, multidisciplinary care. A 14-year-old boy with no significant medical history presented with a 5-day history of fever, altered mental status (Glasgow Coma Scale 6/15), bilateral limb weakness, and sensory deficits. Clinical examination revealed neck stiffness, unequal pupils with a relative afferent pupillary defect, brisk reflexes, and positive Babinski signs. Despite initial management for suspected infectious etiology – —including antibiotics and antitubercular therapy – the patient’s condition rapidly deteriorated. By day 6, the patient developed type II respiratory failure and recurrent seizures, necessitating intensive care measures, including mechanical ventilation. Cerebrospinal fluid analysis showed lymphocytic pleocytosis and elevated protein levels; however, polymerase chain reaction panels for meningoencephalitis and serological tests for anti-myelin oligodendrocyte glycoprotein and anti-aquaporin-4 antibodies were negative. Magnetic resonance imaging of the brain and spinal cord demonstrated extensive demyelination from the midbrain to the upper thoracic region, with T2/FLAIR hyperintensities in subcortical regions [Figure 1].Figure 1: Magnetic resonance imaging (MRI) of the brain and spinal cord demonstrating T2/FLAIR hyperintensities in the basal ganglia, subcortical white matter, and an extensive long segment (from midbrain to upper thoracic level). This imaging finding was pivotal in supporting the diagnosis of severe acute disseminated encephalomyelitis. MRI brain and spinal cord with gadolinium contrast showing: (a) T2/FLAIR hyperintensity in basal ganglia, (b) Optic Neuritis (c) Hyperintensities involving deep white matter of bilateral; frontoparietal, periventricular, occipital and temporal regions (d) A Long segment of altered signal intensities extending from midbrain to T1 vertebral level in spinal cordHigh-dose intravenous methylprednisolone was initiated for 5 days, followed by a tapering regimen. With partial stabilization, immunosuppressive therapy with rituximab was administered in three doses. Supportive care, including seizure management and respiratory support, was crucial for stabilization, though the patient did not achieve full recovery. This case exemplifies the complexity in diagnosing ADEM in the absence of specific biomarkers. The negative serological workup, combined with advanced imaging findings, reinforced the diagnosis of ADEM despite clinical overlap with neuromyelitis optica spectrum disorders. The absence of antibodies against myelin oligodendrocyte glycoprotein and aquaporin-4 highlighted limitations in current diagnostic algorithms, echoing recent literature that reports up to 30% of ADEM cases as seronegative.[1,2] Early recognition and treatment with high-dose corticosteroids remain the cornerstone of ADEM management.[3] In refractory or severe cases, additional immunosuppressive therapies such as rituximab may provide therapeutic benefit, particularly when supported by intensive care interventions.[4] Studies suggest that up to 30% of acute demyelinating encephalomyelitis cases remain seronegative for known biomarkers, underscoring the need for advanced diagnostic modalities.[5] Our case underlines the importance of a multidisciplinary approach given the complications encountered, such as respiratory failure and seizures, which necessitated rapid intervention in the intensive care setting. This case of seronegative ADEM emphasizes the diagnostic challenges in the absence of serological markers and demonstrates that a focused, multidisciplinary strategy – integrating advanced neuroimaging, prompt immunosuppressive therapy, and critical care – can stabilize a critically ill patient. Early intervention is essential to mitigate neurological damage and improve outcomes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Authors: Sachin Bharti, Ritu Singh, Sanjeev Kumar, Alka Kumari
Institution: Indira Gandhi Institute of Medical Sciences
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7118185154