The need for such guidance is rooted in biology. AQP4+ NMOSD and MOGAD are antibody-mediated inflammatory conditions of the central nervous system, but they differ fundamentally in their immunopathology. AQP4 antibodies target a water channel concentrated on astrocytic endfeet, producing lesions that cluster around the ventricles, in the area postrema, and along regions of high aquaporin 4 expression. MOG antibodies, by contrast, attack a myelin surface protein, generating a distinct pattern of demyelination that often involves the optic nerves, spinal cord and, in children, the cerebral cortex. These differences translate into different imaging signatures, different disease courses and different treatment strategies, making accurate radiological interpretation a matter of clinical urgency.

Yet the panel acknowledges that the diagnostic landscape remains treacherous. Imaging features of the two diseases overlap with each other and with multiple sclerosis, lesions evolve in unpredictable ways over time, and acquisition protocols vary widely between centers. A patient presenting with optic neuritis or transverse myelitis may harbor any of these conditions, and the wrong diagnosis can lead to the wrong therapy, with potentially devastating consequences. The new recommendations therefore serve a dual purpose: standardizing practice and sharpening the differential diagnosis at the bedside.

At the heart of the document are standardized protocols. The authors define a core set of MRI sequences that should be performed in every patient, alongside optional sequences for specific clinical questions. Brain MRI, spinal cord imaging and orbital imaging each receive detailed attention, with guidance on the timing of scans at presentation, during acute attacks, and in the follow-up period. The recommendations extend the MAGNIMS framework, long established for multiple sclerosis, into these antibody-mediated diseases, creating a parallel infrastructure for image acquisition and reporting that can be implemented in routine clinical practice.

The characteristic conventional MRI findings of each disease receive careful treatment. In AQP4+ NMOSD, lesions typically affect the spinal cord over long segments, the area postrema causing intractable hiccups and nausea, periependymal surfaces of the ventricles, and the optic chiasm. In MOGAD, longitudinally extensive myelitis is also common but tends to involve the conus medullaris, while optic nerve involvement is frequently anterior and bilateral, and cortical lesions with seizures, including the FLAMES pattern of unilateral cortical FLAIR hyperintensity, point toward MOG antibodies. Recognizing these patterns helps clinicians distinguish the two diseases from each other and from multiple sclerosis, where short-segment cord lesions, central vein signs and paramagnetic rim lesions dominate.

One of the most clinically valuable sections addresses the acute attack. MRI plays a decisive role in determining whether a patient is experiencing a true relapse or a pseudo-relapse, a distinction that changes management entirely. The panel also highlights the phenomenon of radiologic lag in MOGAD, in which brain lesions may appear or evolve days to weeks after the clinical onset of an attack, meaning an early normal scan does not exclude active disease. Serial imaging during the attack window can therefore reveal lesion dynamics that a single time point misses, and the timing of follow-up scans matters as much as their content.

Post-attack recovery is another area where the recommendations break new ground. MOGAD lesions, unlike those of many other demyelinating diseases, have a striking tendency to resolve on T2-weighted images, and the panel discusses the timing and predictors of this lesion resolution. The degree of tissue recovery, visible as the fading of lesions and the relative preservation of tissue volume, carries prognostic weight and informs decisions about how aggressively to treat and how long to continue immunotherapy. Spinal cord atrophy, which correlates with disability in NMOSD, is identified as a key longitudinal measure.

Beyond conventional imaging, the document surveys the added value of non-conventional MRI techniques. Diffusion-based measures, myelin-sensitive sequences, magnetization transfer imaging and volumetric analysis can probe microstructural damage, inflammatory activity and tissue repair that standard T2 and T1 sequences cannot capture. Advanced approaches such as neurite orientation dispersion and density imaging, 7 Tesla imaging of myelin signal in normal-appearing white matter, and even indices of glymphatic system dysfunction are reviewed as research tools that may mature into clinical biomarkers. The panel also points to the emerging role of machine learning and radiomics, including deep learning models trained to distinguish MOGAD from multiple sclerosis, as a frontier for automated diagnostic support.

The recommendations confront one of the field’s most stubborn problems: seronegative NMOSD. Patients who present with the clinical and radiological phenotype of NMOSD but lack detectable AQP4 antibodies form a heterogeneous group whose classification remains uncertain, and whose response to therapy may differ from that of seropositive patients. The panel outlines the diagnostic complexity of this population and argues that novel imaging biomarkers are needed to improve classification and treatment precision, potentially allowing MRI itself to stratify patients when antibody testing is inconclusive.

Ultimately, the consensus document represents a maturing of the field. With targeted therapies now available for both AQP4+ NMOSD and MOGAD, and with growing interest in when immunotherapy can be safely discontinued, standardized imaging is no longer a luxury but a clinical necessity. By codifying what to scan, when to scan and how to interpret the results, the MAGNIMS panel has given neurologists, neuroradiologists and researchers a common language for these diseases, one that should accelerate both better individual care and the multicenter trials needed to push the field forward.

Subject of Research: Consensus recommendations for the use of MRI in diagnosing and monitoring neuromyelitis optica spectrum disorder and MOG antibody-associated disease

Article Title: Use of MRI in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease — MAGNIMS consensus recommendations

Article References: Cortese, R., Hacohen, Y., Arrambide, G., Bianchi, A., DeLuca, G., Filippi, M., Gasperini, C., Geraldes, R., Granziera, C., Haider, L., Messina, S., Sastre-Garriga, J., Preziosa, P., Rocca, M. A., Rovira, A., Tintoré, M., Toosy, A., Tortorella, C., Vaneckova, M., … Schoonheim, M. (2026). Use of MRI in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease — MAGNIMS consensus recommendations. Nature Reviews Neurology. https://doi.org/10.1038/s41582-026-01271-2

Image Credits: AI Generated

DOI: 10.1038/s41582-026-01271-2

Keywords: MRI, NMOSD, MOGAD, aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein, demyelinating disease, neuroimmunology, MAGNIMS, optic neuritis, myelitis, diagnostic criteria, biomarkers

The story begins when a previously healthy five-year-old girl was referred to the neurology unit with a fixed right mydriasis, a persistently dilated pupil, and complete retinal detachment in the same eye. Notably, she had never experienced fever or eye pain, features that might otherwise have steered clinicians toward an infectious or inflammatory process of a different character. Brain magnetic resonance imaging revealed severe right optic neuritis, appearing as hyperintensity on T2-weighted sequences, and serum testing detected anti-MOG antibodies at a low titer of 1:10. On the strength of these findings, the team diagnosed MOGAD, an autoimmune condition in which antibodies target myelin oligodendrocyte glycoprotein, a protein on the surface of myelin sheaths in the central nervous system, and initiated monthly intravenous immunoglobulin at a dose of 2 grams per kilogram.

The initial treatment did not hold the disease in check. Three months later, the girl suffered a brainstem relapse marked by vomiting, dysarthria, and ataxia. Repeat MRI showed contrast-enhancing lesions in both supra- and infratentorial regions, together with tonsillar herniation and obstructive hydrocephalus, a life-threatening buildup of cerebrospinal fluid pressure that required a third ventriculocisternostomy, a surgical bypass procedure. High-dose intravenous methylprednisolone pulses of 20 milligrams per kilogram per day were administered for seven days and produced only partial improvement. Despite ongoing therapy, a further relapse followed just three months later, this time presenting with cerebellar ataxia, dysarthria, and a right foot drop. The clinical picture was that of a refractory, relentlessly relapsing inflammatory disorder of the central nervous system, and the team escalated accordingly.

Faced with this refractory-relapsing MOGAD phenotype, the clinicians turned to rituximab, a monoclonal antibody that depletes CD20-positive B cells and is increasingly used as second-line therapy in antibody-mediated neuroinflammatory disease. The drug was given at 375 milligrams per square meter of body surface area weekly for four weeks, but it was discontinued after yet another relapse. Mycophenolate mofetil at 1000 milligrams per day was then added to the monthly immunoglobulin cycles, and this combination finally produced a more stable remission lasting three years. Even during this quiescent period, however, a subtle clue persisted: the girl’s anti-MOG antibody titers fluctuated, swinging between positive and negative results. The authors emphasize precisely this point in their critique, arguing that the role of MOG-IgG serum titer changes and oscillations should not be solely used to clarify the nature of neuroinflammatory pictures in children.

The remission shattered when the girl was 9.6 years old. She abruptly developed a crossed brainstem syndrome, a pattern of neurological deficits produced by a lesion interrupting nerve tracts and cranial nerve nuclei within the brainstem, manifesting as right lower limb hypertonia, flaccid paralysis of the left arm, anarthria, or complete loss of speech, lingual akinesia, and a fixed rightward deviation of the head. A new brain MRI revealed multiple hemorrhagic lesions lined through the thalamus, the nucleo-capsular regions, and the pons. Hemorrhagic transformation within inflammatory brain lesions of this severity is distinctly unusual for typical MOGAD and signaled that the underlying process was something far more destructive than a conventional demyelinating disease.

At this critical juncture, the clinicians returned to a physical sign that had been present all along: the girl’s silvery-gray hair and eyebrows. This peculiar pigmentation, easily overlooked or attributed to benign variation in a child with an autoimmune diagnosis, is in fact the hallmark of Griscelli syndrome, a group of autosomal recessive disorders defined by partial albinism. Acting on this reassessment, the team performed a molecular testing panel for hemophagocytic lymphohistiocytosis, or HLH, a hyperinflammatory syndrome in which immune cells attack the body’s own tissues and organs, using peripheral blood mononuclear cells. The panel revealed two variants in the RAB27A gene on chromosome 15q21: c.153+5G>A, a splice site variant that alters pre-mRNA splicing, and c.514_518del, a pathogenic five-base-pair deletion.

The molecular findings confirmed Griscelli syndrome type 2, catalogued as OMIM #607623, an ultrarare condition caused by mutations in RAB27A and characterized by partial albinism together with impaired cytotoxic activity of T cells and natural killer cells, carrying a risk of life-threatening hemophagocytic lymphohistiocytosis. The biology connects the two seemingly unrelated features of the case. The Rab27a protein is essential for the release of melanin from melanocytes into surrounding cells; when it is dysfunctional, melanin accumulates abnormally within melanocytes and is not transferred properly, producing the characteristic silvery-gray hair and skin hypopigmentation. The same protein is required for the release of cytolytic granules by cytotoxic lymphocytes, so its absence leaves the immune system unable to eliminate infected or activated cells, permitting uncontrolled immune activation that can culminate in the cytokine storm of HLH.

Importantly, the authors note that HLH may be virtually absent in some patients who present with a completely neurologic phenotype, even when molecular findings are fully consistent with Griscelli syndrome type 2. This phenotypic expansion, previously described in the literature in an eleven-year-old girl with Rab27A mutations and no hemophagocytosis, helps explain why the diagnosis remained hidden for more than five years in the present case. After the genetic confirmation, the girl was started on ruxolitinib, a Janus kinase inhibitor that dampens inflammatory signaling downstream of cytokine receptors, at a dose of 5 milligrams twice daily, and she was placed on the waiting list for hematopoietic stem cell transplantation, the only curative option for this disease. Sadly, a slowly progressive multiorgan failure developed five months later, and the girl died at the age of ten.

The case carries a pointed lesson for pediatric neurologists and immunologists alike. Rare genetic errors of immunity can coexist with hypopigmentation skin disorders, and the authors urge healthcare providers to recall that dysregulated immunity may be camouflaged by devastating neuroinflammatory pictures that begin with something as common as optic neuritis. Autoimmune test results, including anti-MOG positivity, may taint the true disease identity, because a positive MOG test does not automatically mean MOGAD. Low antibody titers, atypical clinical features such as absent pain, hemorrhagic lesions, relapses refractory to appropriately escalated immunotherapy, and fluctuating serology should all prompt a broader differential diagnosis that includes inborn errors of immunity. In such patients, recognizing subtle dysmorphic or pigmentation cues and pursuing molecular panels early can redirect treatment toward targeted immunomodulation and, ultimately, curative transplantation before irreversible damage accumulates.

Published as a letter in response to Aduru and colleagues’ finding that MOGAD is the most common cause of isolated optic neuritis in children, this report does not overturn that conclusion but complicates it. It stands as a reminder that the most frequent explanation is not always the correct one, and that in medicine, as in this child’s silver-gray hair, the most visible clue to a hidden diagnosis may be the one easiest to dismiss.

Subject of Research: Griscelli syndrome type 2 masquerading as MOG antibody-associated neuroinflammatory disease in a child

Article Title: A Lethal Progressive Neuroinflammation Disguised as MOGAD Revealing a Final Diagnosis of Griscelli Syndrome

Article References: Veredice, C., Arpaia, C., Contaldo, I., Capasso, A., & Rigante, D. (2026). A Lethal Progressive Neuroinflammation Disguised as MOGAD Revealing a Final Diagnosis of Griscelli Syndrome. Annals of Clinical and Translational Neurology, 13(8), 1740-1742. https://doi.org/10.1002/acn3.70470

Image Credits: AI Generated

DOI: 10.1002/acn3.70470

Keywords: Griscelli syndrome, MOGAD, optic neuritis, RAB27A, hemophagocytic lymphohistiocytosis, neuroinflammation, pediatric neurology, anti-MOG antibodies, partial albinism, rituximab, ruxolitinob, genetic diagnosis

The research team, led by investigators at Baylor College of Medicine and Texas Children’s Hospital, reviewed the medical records of all pediatric patients diagnosed with MOGAD at their institution between January 2017 and December 2024. To be included, patients had to experience a core clinical demyelinating event and test positive for MOG-IgG antibodies on clinical cell-based assays, with either a clear positive titer of at least 1:100 or a low-positive titer supported by consistent clinical or magnetic resonance imaging features, in line with the international consensus diagnostic criteria established in 2023. Patients with isolated optic neuritis were excluded from the comparison group because their disease course differs fundamentally from other phenotypes and rarely involves seizures, hydrocephalus, or intracranial hypertension.

Of the 124 pediatric patients with MOGAD identified during the eight-year window, 37 required admission to the pediatric intensive care unit, driven by altered mental status, seizures, or the rapid onset of weakness. Sixteen of these critically ill children had to be intubated because of altered consciousness or seizures, with a median duration of mechanical ventilation of three days. Fever was strikingly common in the ICU group, present in 24 of the 37 patients, and cerebrospinal fluid white blood cell counts were significantly higher among those admitted to intensive care compared with those managed on general wards. The ICU cohort also skewed male, and children with the cerebral cortical encephalitis phenotype were dramatically overrepresented, accounting for nearly a third of ICU admissions compared with under five percent of non-ICU cases.

Perhaps the most consequential finding concerns intracranial pressure. Twelve patients showed neuroimaging evidence of increased intracranial pressure, including four with signs of herniation or cerebral shift, five with optic nerve head protrusion and posterior globe flattening in the absence of clinical optic neuritis, and others with sulcal effacement. When the investigators combined imaging evidence, elevated opening pressures on lumbar puncture, and the use of hyperosmolar therapy, they identified 16 unique patients, more than 40 percent of the ICU cohort, with evidence of elevated intracranial pressure. Seven children received hyperosmolar therapy with hypertonic saline, and two underwent placement of invasive intracranial pressure monitoring devices, one of which recorded pressures as high as 50 millimeters of mercury and remained in place for 14 days to guide pharmacologic treatment.

Seizures were another dominant feature of critical MOGAD. Eighteen of the 37 ICU patients experienced seizures, and eleven developed status epilepticus, including one child who met criteria for new-onset refractory status epilepticus, a life-threatening form that resists standard antiseizure medications. Notably, five patients had electrographic seizures visible only on continuous electroencephalography, with no clinical correlate, and all five carried the cerebral cortical encephalitis phenotype. Twenty-seven patients underwent continuous EEG monitoring, revealing a heterogeneous mix of background abnormalities, focal slowing, interictal epileptiform discharges, and rhythmic and periodic patterns on the ictal-interictal continuum, including lateralized and generalized periodic discharges and rhythmic delta activity with and without superimposed spikes. Importantly, the authors found no specific EEG biomarker that reliably distinguishes MOGAD from other autoimmune encephalopathies, contradicting earlier suggestions that the anterior temporal lobe is spared from ictal activity in this disease.

Treatment patterns in the cohort reflected both the promise and the uncertainty of current immunotherapy practice. Most children, 32 of the 37, received immunotherapy during their ICU stay, with intravenous methylprednisolone as the standard first-line agent, alone in 26 cases and combined with intravenous immunoglobulin or plasmapheresis in others. Thirteen patients were adequately treated with first-line therapy, but the remaining nineteen required escalation, most commonly to plasmapheresis or intravenous immunoglobulin, with a median time to escalation of three days. One severely affected child with markedly elevated interleukin-6 levels received the IL-6 receptor antagonist tocilizumab after failing steroids, plasmapheresis, and immunoglobulin, and another received intrathecal dexamethasone. The authors argue that in life-threatening presentations, clinicians should consider early dual immunotherapy, and that emerging data on IL-6 receptor blockade may justify earlier use of tocilizumab in refractory cases.

The study also exposes a diagnostic trap that carries real consequences. Five ICU patients initially received no immunotherapy because their fever and elevated cerebrospinal fluid white cell counts led clinicians to suspect viral encephalitis. Although all five appeared to return to their neurologic baseline without intervention, three later deteriorated and required readmission with new neurologic symptoms before finally receiving immunotherapy. The authors emphasize that fever and cerebrospinal fluid pleocytosis, typically associated with infection, frequently accompany MOGAD attacks and may simply reflect the intensity of neuroinflammation. Their recommendation is that when MOGAD is suspected in a critically ill child, high-dose intravenous steroids should not be delayed while infectious workups proceed in parallel, with infectious disease specialists involved to help weigh the risks.

Outcomes data underscore the stakes of getting this right. Children admitted to the ICU had significantly worse scores on the Functional Status Scale and the Pediatric Cerebral Performance Category scale at follow-up than those managed outside the ICU, were far more likely to require inpatient rehabilitation, and were more than six times as likely to be diagnosed with epilepsy later in life. Intriguingly, the risk of future epilepsy did not correlate with whether a child had seizures or even status epilepticus during the acute illness. Instead, it tracked with evidence of elevated intracranial pressure: 71 percent of children who went on to develop epilepsy had clinical or imaging concern for raised intracranial pressure, compared with just 15.5 percent of those who did not. The authors speculate that secondary cerebral injury, including encephalomalacia and cortical laminar necrosis visible on follow-up MRI, may create the substrate for epileptogenesis, making intracranial hypertension a modifiable target for preventing long-term harm.

The study is not without limitations. Its retrospective design means the clinical approach to assessing and treating intracranial pressure was not standardized, and the authors acknowledge that many patients with evidence of raised pressure did not receive pressure-directed therapy, possibly because the complication was underrecognized in the setting of autoimmune cerebral inflammation. The single-center, tertiary-quaternary referral setting also introduces referral bias. Still, the investigators argue that the findings make a compelling case for systematic neuromonitoring in critically ill children with MOGAD, including routine measurement of opening pressure during lumbar puncture, cautious use of fundoscopy, which proved insensitive in this cohort, and greater adoption of transcranial doppler ultrasonography, which showed elevated middle cerebral artery velocities suggestive of early hyperemia in the four patients tested. They call for early multidisciplinary involvement spanning critical care, neurocritical care, neurosurgery, and infectious disease, and for prospective studies to determine whether aggressive, standardized management of seizures and intracranial pressure can improve the long-term outlook for these children.

Subject of Research: Critical illness, seizures, and intracranial hypertension in pediatric MOG antibody disease requiring intensive care

Article Title: Pediatric MOGAD in the Intensive Care Unit: A Case Series

Article References: Runco, A. D., Davila-Williams, D., Moeller, K. K., Sandweiss, A. J., Ballinger, E., Shukla, N., Riviello, J. J., Erklauer, J. C., & Fisher, K. S. (2026). Pediatric MOGAD in the Intensive Care Unit: A Case Series. Neurocritical Care. https://doi.org/10.1007/s12028-026-02653-6

Image Credits: AI Generated

DOI: 10.1007/s12028-026-02653-6

Keywords: MOGAD, pediatric neurology, neurocritical care, intracranial pressure, status epilepticus, demyelinating disease, continuous EEG, immunotherapy, cerebral cortical encephalitis, ADEM, epilepsy risk, intensive care