Multimodal evoked potentials are useful for the diagnosis of pediatric acute disseminated encephalomyelitis.

BACKGROUND: The application of evoked potentials (EPs) to the diagnosis of acute disseminated encephalomyelitis (ADEM ) has not been investigated in detail. The aim of this study, therefore, was to analyze the value of multimodal EPs in the early diagnosis of pediatric ADEM. METHODS: This was a retrospective study in which we enrolled pediatric ADEM patients and controls (Cs) from neurology units between 2017 and 2021. We measured indices in patients using brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs), and then we analyzed their early diagnostic value in ADEM patients. RESULTS: The mean age of the ADEM group was 6.15 ± 3.28 years (range,1-12 years) and the male/female ratio was 2.1:1 The mean age of the Cs was 5.97 ± 3.40 years (range,1-12 years) and the male/female ratio was 1.3:1. As we used magnetic resonance imaging (MRI) as the diagnostic criterion, the sensitivity, specificity, and accuracy (κ was 0.88) of multimodal EPs were highly consistent with those of MRI; and the validity could be ranked in the following order with respect to the diagnosis of ADEM: multimodal Eps > single SEP > single VEP > single BAEP. Of 34 patients with ADEM, abnormalities in multimodal EPs were 94.12%, while abnormalities in single VEPs, BAEPs and SEPs were 70.59%,64.71%and 85.3%, respectively. We noted significant differences between single VEP/BAEPs and multimodal EPs (χ2 = 6.476/8.995,P = 0.011/0.003). CONCLUSIONS: The combined application of multimodal EPs was superior to BAEPs, VEPs, or SEPs alone in detecting the existence of central nerve demyelination, and we hypothesize that these modalities will be applicable in the early diagnosis of ADEM.

Postdengue Acute Disseminated Encephalomyelitis.

A 38-year-old gentleman, following an uncomplicated dengue fever 2 weeks back, developed acute onset bilateral lower limb weakness and numbness for 5 days, associated with bladder and bowel incontinence and a band-like sensation in T4 dermatome. On examination, he had paraparesis with normal cranial nerves except for left upper motor neuron-type 7th cranial nerve palsy and normal higher mental function. Magnetic resonance imaging (MRI) of the brain and spine detected multiple demyelinating lesions. A diagnosis of postdengue acute disseminated encephalomyelitis (ADEM) was made as part of postinfective inflammatory process after the fever had subsided. Cerebrospinal fluid study ruled out active infection. He was treated with intravenous steroids and is currently recovering. An interesting point in our case was that the patient had significant imaging findings in MRI of the brain with no symptoms or signs suggestive of intracranial involvement-ADEM without evidence of encephalitis.

Recurrent Acute Disseminated Encephalomyelitis Presenting as Conus Medullaris Syndrome: A Case Report.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that typically follows an infection or recent vaccination. Symptoms such as encephalopathy and focal neurological deficits appear weeks after the initial illness, leading to swift and progressive neurological decline. While ADEM in the brain has been well documented, reports of ADEM, specifically in the spinal cord, are relatively limited. A 58-year-old male presented with rapidly progressive bilateral lower extremity tingling, numbness, and mild gait disturbance approximately two days prior to visiting the emergency room. Spinal magnetic resonance imaging revealed a diffuse, longitudinal, high-signal lesion with mild enlargement of the conus and proximal cauda equina. The lesions were predominantly localized in the distal conus and cauda equina, and serial electrodiagnostic studies showed that the lesions progressed toward the proximal conus in tandem with symptom evolution and lacked clear lateralization. The patient was subsequently treated with high-dose steroids for seven days (intravenous methylprednisolone, 1 mg/kg). The patient's lower extremity weakness gradually improved and he was able to walk independently under supervision three weeks after symptom onset. In this case of spinal ADEM in a middle-aged adult, high-dose steroid treatment led to outstanding neurological recovery from both the initial occurrence and subsequent attacks.

Acute disseminated encephalomyelitis in a patient with monkeypox: a case report and radiological findings.

Monkeypox is a zoonosis caused by a double-stranded DNA virus of the Poxviridae family. It currently represents a global epidemic given its contagion reported in more than 31 previously non-endemic countries. We present the case of a 30-year-old male patient from Peru with a diagnosis of monkeypox by PCR test, who manifested an initial clinical picture of asthenia, adynamia, and odynophagia, with the appearance of pustular lesions on the lower lip and in the genital region associated with motor and sensory deficit of the lower limbs with altered state of consciousness, with subsequent findings of acute disseminated encephalitis by brain magnetic resonance imaging. This entity corresponds to an infrequent complication with only one case reported in the literature. The importance lies in knowing the possible imaging findings to suspect the diagnosis and expand the knowledge about this current disease.

[Catatonia as an initial presentation of acute disseminated encephalomyelitis]. / Katatonie als initiële uiting van acute gedissemineerde encefalomyelitis.

We describe a case of a 36-year-old woman with no psychiatric or somatic history who was presented to the emergency department with a profound change in mental status, more precisely a catatonic status and auditory hallucinations. Due to the unclear aetiology and suspicion of underlying psychiatric problems, the patient was admitted to the psychiatric ward. After discharge against medical advice, readmission was necessary due to deterioration and sudden onset of myoclonus. On further examination, acute disseminated encephalomyelitis (ADEM) was diagnosed. This case illustrates that ADEM can present itself as an initial psychiatric problem and emphasizes the importance of extensive medical clearance at presentation and continued attention for possible somatic origin, even when the initial clearance turns out to be negative.

Serum neurofilament light-chain levels in children with monophasic myelin oligodendrocyte glycoprotein-associated disease, multiple sclerosis, and other acquired demyelinating syndrome.

OBJECTIVE: To assess the diagnostic and prognostic potential of serum neurofilament light chain (sNfL) in children with first acquired demyelinating syndrome (ADS). METHODS: We selected 129 children with first ADS including 19 children with myelin oligodendrocyte glycoprotein (MOG)-antibody associated disease (MOGAD), 36 MOG/AQP4-seronegative ADS, and 74 with multiple sclerosis (MS) from the BIOMARKER study cohort. All children had a complete set of clinical, radiological, laboratory data and serum for NfL measurement using a highly sensitive digital ELISA (SIMOA). A control group of 35 children with non-inflammatory neurological diseases was included. sNfL levels were compared across patient groups according to clinical, laboratory, neuroradiological features and outcome after 2 years. RESULTS: sNfL levels were significantly increased in MOGAD, seronegative ADS and MS compared to controls (p-value < 0.001), in particular in children with an acute disseminated encephalomyelitis (ADEM)-like magnetic resonance imaging (MRI) pattern (p < 0.001) or longitudinally extensive myelitis (p < 0.01). In pediatric MS, elevated sNfL levels were significantly associated with higher numbers of cerebral (p < 0.001) and presence of spinal (p < 0.05) MRI lesions at baseline and predicted a higher number of relapses (p < 0.05). CONCLUSION: sNfL levels are significantly elevated in all three studied pediatric ADS subtypes indicating neuroaxonal injury. In pediatric MS high levels of sNfL are associated with risk factors for disease progression.

Acute disseminated encephalomyelitis (ADEM) following recent Oxford/AstraZeneca COVID-19 vaccination.

This report describes the clinical context and autopsy findings in the first reported fatal case of acute disseminated encephalomyelitis (ADEM), developed after being vaccinated using the Oxford/AstraZeneca COVID-19 vaccine. ADEM is a rare autoimmune disease, causing demyelination in the brain and spinal cord. A wide variety of precipitating factors can trigger ADEM, and it has long been known to be a rare adverse event following some types of vaccinations. Recently, ADEM has also been associated with COVID-19 infection and (very rarely) with COVID-19 vaccination. The reports of the latter however all pertain to living patients. Our case demonstrates that ADEM should be considered in patients developing neurological symptoms post COVID-19 vaccination, although that this adverse reaction is likely to remain extremely rare. Our report further emphasizes the added value of comprehensive post mortem investigation to confirm ante mortem diagnosis and to determine vaccination safety.

Acute disseminated encephalomyelitis.

ABSTRACT: Acute disseminated encephalomyelitis (ADEM) is a relatively rare autoimmune process that causes demyelination of the central nervous system. This condition primarily affects children under age 10 years and can produce symptoms including fever, vomiting, headaches, and altered mental status. Diagnostic criteria include encephalopathy (behavioral changes or altered mental status not explained by fever) and MRI findings of demyelination during the first 3 months of developing symptoms without subsequent new MRI findings. Patients can have full recovery within days to weeks if recognized and treated promptly. This article describes an ED visit and hospital course for a 3-year-old girl with headaches and fatigue who was diagnosed with and treated for ADEM.

Atypical Presentation of Fulminating Subacute Sclerosing Panencephalitis: A Case Series.

Subacute sclerosing panencephalitis (SSPE) is a rare and progressive inflammatory disease of central nervous system due to aberrant measles virus with an outcome that is nearly always fatal. In acute fulminant SSPE, the disease rapidly evolves leading to death within 3 months of the diagnosis. We report here four cases of fulminant SSPE with atypical presentations, two of them presented at very early age with history of congenital measles infection in first case and gait abnormality as initial symptom in second case; acute disseminated encephalomyelitis (ADEM) with refractory seizures in third case, unilateral myoclonus with hemiparesis in fourth case at the onset of disease, respectively. The typical periodic electroencephalographic (EEG) complexes, elevated cerebrospinal fluid (CSF), and serum antimeasles antibodies in our patients led to the diagnosis of SSPE. A high index of clinical suspicion in fulminant type with awareness of atypical features, EEG, and CSF studies are of paramount importance in establishing its diagnosis.

Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation.

AIM: To explore the cerebrospinal fluid (CSF) metabolite features in acute neuroinflammatory diseases and identify potential biomarkers to diagnose and monitor neuroinflammation. METHOD: A cohort of 14 patients (five females, nine males; mean [median] age 7y 9mo [9y], range 6mo-13y) with acute encephalitis (acute disseminated encephalomyelitis n=6, unknown suspected viral encephalitis n=3, enteroviral encephalitis n=2, seronegative autoimmune encephalitis n=2, herpes simplex encephalitis n=1) and age-matched non-inflammatory neurological disease controls (n=14) were investigated using an untargeted metabolomics approach. CSF metabolites were analyzed with liquid chromatography coupled to high resolution mass spectrometry, followed by subsequent multivariate and univariate statistical methods. RESULTS: A total of 35 metabolites could be discriminated statistically between the groups using supervised orthogonal partial least squares discriminant analysis and analysis of variance. The tryptophan-kynurenine pathway contributed nine key metabolites. There was a statistical increase of kynurenine, quinolinic acid, and anthranilic acid in patients with encephalitis, whereas tryptophan, 3-hydroxyanthrnailic acid, and kynurenic acid were decreased. The nitric oxide pathway contributed four metabolites, with elevated asymmetric dimethylarginine and argininosuccinic acid, and decreased arginine and citrulline in patients with encephalitis. An increase in the CSF kynurenine/tryptophan ratio (p<0.001), anthranilic acid/3-hydroxyanthranilic acid ratio (p<0.001), asymmetric dimethylarginine/arginine ratio (p<0.001), and neopterin (p<0.001) strongly predicted neuroinflammation. INTERPRETATION: The combination of alterations in the tryptophan-kynurenine pathway, nitric oxide pathway, and neopterin represent a useful potential panel for neuroinflammation and holds potential for clinical translation practice. WHAT THIS PAPER ADDS: The kynurenine/tryptophan and anthranilic acid/3-hydroxyanthranilic acid ratios hold great potential as biomarkers of neuroinflammation. Elevation of the asymmetric dimethylarginine/arginine ratio in acute brain inflammation shows dysregulation of the nitric oxide pathway.

Rare and Atypical Presentations of Acute Disseminated Encephalomyelitis in Children: A Case Series.

Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disorder of central nervous system occurring in children with a wide range of clinical manifestations after infection or vaccination. There are few case reports in literature, describing atypical presentations of ADEM with fever of unknown origin, autonomic dysfunction, complex movement disorders such as myoclonus, dystonia and chorea, acute psychosis and myocarditis. Here, we report four cases of ADEM with atypical features like uniocular blindness, myelin oligodendrocyte glycoprotein antibodies negative multiphasic disseminated encephalomyelitis, ADEM mimicking Guillain-Barre syndrome at presentation and isolated spinal ADEM. Treatment with high-dose steroids elicited an excellent neurological outcome in all patients. A high index of clinical suspicion along-with awareness of atypical features, magnetic resonance imaging and cerebrospinal fluid studies are of paramount importance in establishing ADEM diagnosis and initiation of early treatment for better outcome.

A unique finding of the basilar artery.

Variants of the posterior intracranial circulation are important for surgeon, interventionalists and radiologists. Herein, a unique configuration of the basilar artery is reported. A 54-year-old man with a history of COPD, hypothyroidism, smoking, and hyperlipidemia presented to an outside institution with nausea, confusion, altered mental status, and ataxia. The patient was evaluated for stroke. Imaging revealed rotation of the basilar apex of 180 degrees, fetal configuration of the posterior communicating artery, right posterior cerebral artery filling from the left vertebral artery, and duplication of the left and right superior cerebellar arteries. The patient continued to deteriorate neurologically and MRI revealed multifocal and symmetric signal abnormalities in the brain stem, thalami, basal ganglia, and hippocampi. The differential diagnosis included acute disseminated myeloencephalitis. Despite plasma exchange and steroid therapy, the patient died a few days later. This case report demonstrates a rare variation of the basilar apex.

Case of Acute Disseminated Encephalomyelitis Associated with Cytomegalovirus Reactivation in an Immunocompromised Systemic Lupus Erythematosus Patient.

We present a case of an immunocompromised systemic lupus erythematosus female patient admitted to our hospital for general impairment, monoparesis, and temporary cognitive disability. The case represented a significant diagnostic and therapeutic challenge primarily because of a wide range of differential diagnosis options (CNS lupus, ischemic cerebrovascular disease, viral meningoencephalitis, progressive multifocal leukoencephalopathy, limbic encephalitis, and acute disseminated encephalomyelitis-ADEM). Brain MRI findings were compatible with ADEM, and microbiological tests showed a cytomegalovirus infection (CMV) which is rarely associated with ADEM despite the increasing number of immunocompromised patients prone to symptomatic CMV reactivation. Our patient was treated with intravenous methylprednisolone, immunoglobulin (IVIG), along with antiviral therapy resulting in a favorable therapeutic effect. In conclusion, only a few described ADEM cases have been associated with CMV, and none of them, to the best of our knowledge, in an immunocompromised patient. In this case, a multidisciplinary approach and broad diagnostic considerations were decisive for successful treatment and outcome.

[Acute disseminated encephalomyelitis and myelitis associated with new coronavirus infection COVID-19. Case report].

Acute disseminated encephalomyelitis (AEM) and acute transverse myelitis (OPM) are autoimmune demyelinating diseases of the central nervous system. Two clinical observations of AEM and OPM developed after suffering acute coronavirus infection (SARS-CoV-2) are presented. Differential diagnosis was carried out with multiple sclerosis, encephalitis of an infectious nature, compressive myelopathy, and opticomyelitis. Both observations show an almost complete recovery of lost functions. The pathogenetic mechanisms of the development of AEM and OPM in patients with coronavirus infection are discussed. The onset of central nervous system dysimmune lesion in the context of coronavirus infection makes it necessary to monitor the clinical situation with the involvement of a neurologist for timely diagnosis and determination of therapeutic tactics that can reduce the degree of disability of patients.

Listeria rhombencephalitis mimicking acute disseminated encephalomyelitis in a patient without predisposing medical conditions.

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.

Bilateral thalamic lesions in a patient with probable acute disseminating encephalomyelitis: a case report.

BACKGROUND: Bilateral thalamic lesions are rare. Here, we describe a case of probable acute disseminating encephalomyelitis (ADEM) with symmetrical bilateral thalamic lesions. CASE PRESENTATION: An 85-year-old man presented with weakness of the lower limbs and urinary retention for 1 day, soon followed by coma. He had an H1N1 influenza vaccination 3 months ago. A lumbar puncture showed positive oligoclonal bands and negative results for anti-AQP4 antibodies. A head MRI demonstrated focal symmetrical bilateral thalamic lesions. An MRI of the thoracic spinal cord showed longitudinally extensive lesions in the spinal cord. He was diagnosed with probable ADEM. Despite being treated with IVIG, the patient remained unconscious and died a month later from pneumonia. CONCLUSIONS: In cases with bilateral thalamic lesions, the possibility of ADEM should be considered. The characteristics of the thalamic lesions and imaging findings in other parts of the brain or spinal cord should be taken into account in association with the clinical and laboratory information in making a correct diagnosis.

Acute Disseminated Encephalomyelitis followed by Optic Neuritis: A Rare Syndrome of Uncertain Treatment and Prognosis.

AIM: Acute Disseminated Encephalomyelitis followed by optic neuritis (ADEM-ON), first described in 2013, is a rare demyelinating syndrome, typical of the pediatric age. We conducted a mini review of the existing literature, focusing on clinical, laboratory, radiological, therapeutic, and prognostic aspects in order to improve the identification of new cases. METHODS: We searched PubMed and Cochrane Library for studies on ADEM-ON between 2013 and 2018. RESULTS EXAMINATION: of the reported cases (three case reports and eight observational studies) established the following features. Time between ADEM and ON is highly variable. Almost all patients show antimyelin oligodendrocyte glycoprotein antibody (MOG-abs) seropositivity. High-dose intravenous steroid and plasmapheresis efficacy is reported for the acute phase; oral prednisone and other maintenance drugs may be useful in avoiding relapses. The clinical history may lead to a complete recovery but also to residual deficits. CONCLUSION: MOG-abs detection strongly supports ADEM-ON diagnosis, confirming this entity as part of MOG-abs spectrum disorder. Owing to the very small number of cases so far reported, predicting clinical evolution is very difficult.

Possible clinical role of MOG antibody testing in children presenting with acute neurological symptoms.

The differential diagnosis between acquired inflammatory demyelinating syndromes of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and acute disseminated encephalomyelitis (ADEM) can be very challenging at onset. Apart from cerebrospinal fluid oligoclonal bands and anti-aquaporin-4 antibodies (AQP4-Ab), definite diagnostic biomarkers are lacking. Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) have been increasingly described in children with AQP4-seronegative NMOSD, ADEM and other inflammatory demyelinating CND syndromes; despite partial overlaps with AQP4-Ab disease, a novel "MOG-Ab-disorder" phenotype has been suggested. In this study, we tested the presence of MOG-Ab and AQP4-Ab in 57 children at first onset of acute neurological symptoms; three clinical subgroups were identified: 12 patients had acquired inflammatory demyelinating CNS syndromes, 11 had other autoimmune/immune-mediated disorders of the central and peripheral nervous system and 34 had non-immune-mediated CNS disorders. MOG-Abs were found positive only in a subset of cases in the subgroup with acquired inflammatory demyelinating CNS syndromes (in 2/12 patients, both with non-MS phenotype) and in none of the patients with other autoimmune and immune-mediated disorders of the central and peripheral nervous system or with non-immune-mediated disorders of the CNS.Data from the literature review support clinical and analytical observations.

Zika virus found in brain tissue of a multiple sclerosis patient undergoing an acute disseminated encephalomyelitis-like episode.

BACKGROUND: A range of different neurological manifestations has been reported in fetuses and adults after Zika virus (ZIKV) infection. OBJECTIVE: We describe a detection of the ZIKV in the brain tissue from a multiple sclerosis (MS) patient with acute disseminated encephalomyelitis (ADEM)-like event in Rio de Janeiro, Brazil. METHODS: Biological samples collected during the hospitalization were tested by serology and molecular diagnostic for various infectious agents. Histopathological analysis was performed using the anti-flavivirus group 4G2 monoclonal antibody, anti-ZIKV non-structural 1 (NS1) monoclonal antibody, and anti-CD4, CD8, and CD11b antibodies. RESULTS: Anti-ZIKV IgM and IgG antibodies were positive in the serum and urine. A brain biopsy showed ZIKV protein in brain cells and T CD8 infiltration in brain tissue. CONCLUSION: Our data describe the coexistence of a recent central nervous system (CNS) ZIKV infection accompanied by a severe ADEM-like syndrome outcome in a patient with clinical history of MS. A de novo immune response concomitant with ZIKV infection might be involved in the mechanism of the ADEM-like syndrome and response to immunotherapy. The present report reinforces the importance of providing the differential diagnosis of acute episodes of MS exacerbation in an environment prone to ZIKV expression.

Paediatric MOG antibody-associated ADEM with complex movement disorder: A case report.

Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are a well-recognized cause of acquired demyelinating syndromes in both adult and children. Despite basal ganglia involvement on imaging, movement disorder is not a cardinal feature. We describe a 2-year-9-month-old girl who presented with severe encephalopathy with aphasia, seizures and a complex movement disorder with dystonic posturing and tonic eye deviation. Neuroimaging revealed subtle asymmetrical predominantly white matter signal changes. MOG-Abs were positive in the serum. Other known pathogenic autoantibodies including N-methyl-D-aspartate receptor antibodies (NMDAR-Abs) were negative. The patient made a complete recovery following 2-week corticosteroid treatment. This case highlights the need for MOG-Ab testing in children with suspected autoimmune encephalopathies.