Disseminated Encephalomyelitis Research Articles

Neurologic manifestations and COVID-19

In the article by Jiménez-Ruiz et al., entitled “Neuro-logic manifestations of COVID-19”,1 it was concluded that “we must bear in mind infectious and non-infec-tious complications that affect the nervous system such as encephalitis, seizures, Guillain-Barre syndrome, dis-seminated encephalomyelitis and hemorrhagic leuko-encephalitis, which are disorders that can occur during or after viral infections.

Клінічні особливості уражень нервової системи у хворих з моноінфекцією EBV і в асоціації з іншими герпесвірусами при їх реактивації та персистенції

Під спостереженням перебувало 48 хворих з ураженнями нервової системи, викликаними вірусами Епштейна — Барр (EBV) у моноінфекції або в асоціації з іншими вірусами родини герпесу при їх реактивації або персистенції. При активації EBV-інфекції найчастіше діагностується арахноїдит — 29,4 % і арахноенцефаліт — 26,5 %, рідше розсіяний енцефаломієліт — 11,8 % та енцефаліт — 11,8 %, енцефалополінейропатія — 5,9 %, менінгоенцефаліт — 5,9 %. При персистенції вірусів родини герпесу енцефаліт не діагностовано, арахноїдит був у 28,6 %, арахноенцефаліт — у 28,6 %, розсіяний енцефаломієліт — у 14,3 %. Показана різниця виявлення неврологічних симптомів і синдромів у групі хворих з активацією та реактивацією порівняно з персистенцією.

Vitamin D and neurospecific proteins in children with inflammatory demyelinating diseases of central nervous system

The relevance of studying the provision of vitamin D in children with inflammatory diseases of the central nervous system (CNS) is due to a high prevalence of vitamin D deficiency conditions in children population, which, according to current literature data, leads to the imbalance of the immune system and a predisposition to a severe disease course, chronization of the process, development of autoimmune pathology. The study of the concentration of neurospecific proteins (NSP) in blood serum and cerebrospinal fluid (CSF) has been recently used to analyze the degree and nature of nervous tissue damage in case of various CNS diseases. The study included investigation of blood serum and CSF samples obtained from 107 children (34 – with encephalitis, 28 – with disseminated encephalomyelitis (DEM), 20 – with multiple sclerosis (MS), 25 – control group). Determination of vitamin D levels (25(OH)D) was performed by the method of electrochemiluminescence immunoassay, concentrations of myelin basic protein, neuron-specific enolase, S100 protein and glial fibrillary acidic protein – by ELISA method. A decrease in the concentration of vitamin D under 30 ng/ml was found in 95% of children with inflammatory diseases of the central nervous system, while the severity of the deficiency of 25(OH)D was associated with the severity of the disease course. In the early stages of the disease in all groups, a significant increase in the level of the main myelin protein was found, while an increase in the concentration of other NSP was observed less frequently and was associated with a severe and complicated course of the disease. Correlations of different intensity and direction between NSP and 25(OH)D were found, which indicates their importance in the pathogenesis of inflammatory diseases of CNS.

Comparative characteristic of laboratory indicators for encephalitis, disseminated encephalomyelitis and multiple sclerosis in children

Background. The similarity of the clinical manifestations of encephalitis (E), disseminated encephalomyelitis (DEM) and multiple sclerosis (MS) in children, the complexity of predicting the nature of the course and outcome of diseases determines the search for additional diagnostic and prognosis criteria.Objective: a comparative characteristic of laboratory indicators for E, DEM and RS in children to assess their diagnostic and prognostic value.Materials and methods. Fifty six children (14 children with E, 14 – with DEM, 28 – with MS) and 16 children of the control group (with acute respiratory virus infection) at the age from 10 to 17 years were examined. Laboratory methods included standard studies of cerebrospinal fluid (protein, cytosis), determination of concentrations of albumin and immunoglobulin G (IgG) in cerebrospinal fluid and serum with subsequent calculation of protein indices (albumin, immunoglobulin, intrathecal immunoglobulin G indexes).Results. With all nosological forms in the serum there were no significant differences between albumin and IgG from the control group, whereas in the cerebrospinal fluid an excess of the concentration of IgG was detected at a normal level of albumin. An increase in the albumin index was found only in E, whereas the immunoglobulin index was significantly higher than the norm in all groups of patients. A significant spread of the intrathecal IgG index (from 0.1 to 11.9) was found, which determined the analysis of clinical and laboratory parameters by subgroups, depending on its magnitude. The maximum incidence of increased intrathecal IgG synthesis was detected in children with MS (with exacerbation of MS – 74 %, in remission – 67 %), whereas in E and DEM, an increase was observed in about half of the patients surveyed and associated with a more favorable course of the disease.Conclusion. The data obtained make it possible to assert that, despite the commonness of some pathogenetic mechanisms, there are differences in the degree of impaired permeability of the blood brain barrier, the intensity of the systemic and intrathecal humoral immune response in E, DEM and RS, which may determine the features of their course and the outcome of the disease, including the transformation of the DEM in the RS.

MRI AND EVOKED POTENTTIALS IN DIFFERENTIAL DIAGNOSIS OF ENCEPHALITIS, DISSEMINATED ENCEPHALOMYELITIS AND MULTIPLE SCLEROSIS IN CHILDREN

Last years are characterized by the growth of encephalitis (Ef) frequency and demyelination diseases of CNS in children, especially, among teenagers. The diseases are characterized by similar of clinical features of the disease onset, absence of differential diagnostical criteria and frequency of the disease chronisation and possibility of transformation in multiple sclerosis (MS), all this determines the problem of differential diagnosis. The aim is to determine differential-diagnostical features of Ef, disseminated encephalomyelitis (DEM) and MS in children by analysis of structure MRI and brain multi-modal evoked potentials (MEP). We observed 35 children with Ef, 40 with DEM and 40 with MS. All patients were from 3 to 17 years old. All patients were diagnosed clinically in acute period and in catamnesis — after 3 and 6 months. MS diagnosis was based on McDonald criteria, 2010 year. ADEM diagnosis was also based on international criteria. We analyzed brain MRI, spinal MRI and MEP in all patients during the first day of hospitalization and after 3 and 6 months later. The analysis of the MRI of the brain and spinal cord in encephalitis (EF, n=35), disseminated encephalomyelitis (ADEM, n=60) and multiple sclerosis (MS, n=60) of children on admission to hospital, and then — after 3 and 6 months. Up to 85% of foci with ADEM and EF had irregular shapes, accompanied by swelling phenomena, and mass effect and in 2⁄3 cases were localized in the gray or white and gray matter of the CNS. In 60% of cases in patients with EF and ADEM based on the localization of foci could suggest the etiology of the disease. In MS 67,5% were detected multifocal white matter lesions (more than 10 lesions), and most of the foci had a size of up to 1 cm and the correct round-oval and the absence of signs of inflammation. The presence of lesions in the gray matter at EF, ADEM and MS respectively observed in 82,5%, 40% and 7,5% of cases. After 3–6 months of MRI in the majority of EF and DEM foci regressed, and in MS were reduced in size, but not completely disappeared. According to the study of evoked potentials (EP) of the brain in children with MS and ADEM often increased latency of the responses, while the EF decreased cortical or brainstem response amplitude. The majority of patients with MS have changed the parameters both 3–4 different EP (somatosensory from the upper and lower limbs, acoustic stem and/or visual), while ADEM and EF-1–2 evoked potentials. Chronic EF, and the progression of neurological symptoms was not associated with the advent of the «new» lesion, and up to 75% of the foci can regress completely after 3–6 months. Chronic EF characterized by increase of only brain atrophy, which involves communication of these changes only with neuronal process. Whereas in MS and multiphase ADEM appeared «new» foci accumulating contrast agent that allows you to talk about preserving the pathogenesis of vascular component in their progression. Study of MEP and MRI in children with Ef, DEM and MS in dynamics can be useful for differential diagnosis and monitoring of therapy efficacy.

Disseminated encephalomyelitis in children

The advent of MRI has contributed to increase the interest and awareness in childhood white matter disorders. A major priority is to distinguish transient and self-limited demyelinating syndromes like disseminated encephalomyelitis (DEM), from life-long diseases like multiple sclerosis (MS). However, the term DEM has been inconsistently applied across studies due to the lack of clear clinical and neuroimaging diagnostic criteria. The present review summarizes the available literature on DEM in children, outlines the main clinical and neuroimaging features at presentation, pathogenesis and outcome, and its differentiation from other conditions with acute impact in the CNS. The recently proposed clinical definitions for monophasic disseminated encephalomyelitis and its relapsing variants are discussed, and controversies surrounding the diagnosis of MS in children are addressed.

Disseminated Encephalomyelitis and Multiple Sclerosis Differentiation

The distinguishing features of acute disseminated encephalomyelitis (DEM) and multiple sclerosis (MS) are reviewed by researchers at Harvard Medical School, Boston, MA, and University of Zagreb, Croatia.

Disseminated encephalomyelitis and multiple sclerosis: two different diseases ? a critical review

The practice of initiating immunomodulatory treatment immediately after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) emphasizes the need to distinguish between disseminated encephalomyelitis (DEM) and MS. Their clinical, genetic, imaging, and histopathological characteristics establish that they are distinct disease entities. Acute and recurrent DEM are more common in children, but also occur in adults. DEM is polysymptomatic and includes signs and symptoms rarely encountered in MS, such as fever, alterations of the state of consciousness, cognitive and aphasic symptoms, and meningism. Cerebrospinal oligoclonal bands are rare. Magnetic resonance imaging (MRI) is the best means of distinguishing between DEM and MS. In the former, the lesion load is heavy, thalamus or basal ganglia are often affected, and early in the disease most of the lesions are usually larger than those of MS and enhance with gadolinium. The MRI spinal cord lesions are longer than three vertebral segments, and define neuromyelitis optica (NMO). Antibodies against aquaporin-4 are present in some NMO, but are also found in cases of MS and DEM. Most NMO are forms of DEM, not MS, and are identical with the 'Oriental' or 'optico-spinal' form of MS.

Multiphasic disseminated encephalomyelitis, systemic lupus erythematosus and antiphospholipid syndrome

We report a case of multiphasic disseminated encephalomyelitis (MDEM) associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The initial presentation was suggestive of multiple sclerosis. Further clinical attacks, MRI imaging, and CSF findings led to a diagnosis of disseminated encephalomyelitis (DEM). Multiple episodes of neurological dysfunction, which differed in clinical presentation, further categorized the diagnosis as multiphasic DEM. The co-occurrence SLE and antiphospholipid syndrome is unusual and provided an additional diagnostic challenge.

The spectrum of disseminated encephalomyelitis

Disseminated encephalomyelitis (DEM) is the acute or chronic response of the immune system to an antigen. It is noteworthy that it can affect simultaneously the central and peripheral portions of the nervous system, the latter clearly differentiating it from multiple sclerosis (MS). Pathologically there are differences and gradations in the type and severity of damage that are seen mostly, although not exclusively, in the white matter. Although DEM is generally considered to be a demyelinating disease, edema and inflammation, and even hemorrhage, are not only major constituents of the pathological response but may, in some instances, be its only manifestations. DEM can be seen following a wide variety of viral infections and vaccinations ; the acute phase generally occurs within one to three weeks after the precipitating event. In rare instances, it may occur in a matter of hours or days, or as late as several months, after a dated antigenic challenge such as a vaccination. Unfortunately, the recurrent or multiphasic, or the unusual progressive, forms of DEM are rarely recognized in adults in whom they are frequently misdiagnosed as MS, despite the fact that they are just as common as they are in children. Except for fever, headache, nausea and vomiting, alterations in the state of consciousness and cognitive abnormalities, the central nervous system symptoms of DEM, are very similar to those of MS. It is important to note that the triggering infection may be very mild or it may be subclinical and escape attention. Magnetic resonance imaging (MRI) has made it possible to correctly diagnose DEM in its acute, chronic, recurrent and multiphasic forms because, in most instances, the images are quite typical. Nevertheless, in clinical practice, the images of DEM and MS are often confused resulting in the former being misdiagnosed as the latter, resulting in the inappropriate initiation of long-term immunomodulatory treatment. This review will illustrate different clinical and MRI presentations of DEM in order to emphasize the features which help to differentiate it from MS.

CNS demyelination in autoimmune diseases

Autoimmune diseases represent a diverse group of disorders that have generally of unknown etiology and poorly understood pathogenesis. They may be organ-specific or systemic, giving rise to overlapping syndromes; more than one autoimmune disease may occur in the same patient. Numerous case reports have documented that multiple sclerosis (MS) may be present concurrently with other autoimmune diseases, most commonly rheumatoid arthritis, autoimmune thyroid disease, type I diabetes mellitus and pernicious anemia. Case reports of disseminated encephalomyelitis (DEM) coincidental with other autoimmune diseases are rare. Many of systemic autoimmune diseases cause central nervous system (CNS) demyelination and are frequently then diagnosed as MS, whereas they often are instances of DEM, the result of vascular, granulomatous or postinfectious manifestations. We have reviewed 15 patients with autoimmune diseases and CNS demyelination in order to determine the nature of the demyelinating process.

Non-MS recurrent demyelinating diseases

The introduction of MRI has shown that the acute, recurrent (R), and multiphasic (M) forms of disseminated encephalomyelitis (DEM) are more common than suspected in adults, and that their MR images are sufficiently characteristic in most instances to make differentiation from multiple sclerosis (MS) possible. In addition, a number of clinical features of DEM are rarely seen in MS: fever, malaise, nausea, vomiting, positional vertigo, convulsions, aphasia, meningism, bilateral optic neuritis, and CSF leukocytosis and elevated protein. CSF oligoclonal bands are usually absent. It is remarkable that confusion between R- and MDEM and MS persists despite the numerous published reports on recurrent DEM dating back 70 years, many illustrating the characteristic MRIs. There are many case reports of DEM erroneously diagnosed as MS, Schilder’s, Marburg’s, Devic’s, and Baló’s disease, and, in particular brain tumors. It is probable that acute DEM is occasionally mistaken for a clinically isolated symptom of MS. Possible mechanisms for recurrence include localization at the site of a previous injury to the nervous system, or by the phenomenon of molecular mimicry. The importance of differentiating R- and MDEM from MS is greater today due to the recommendation that immunodulatory treatment be initiated in patients with a clinically isolated syndrome, or when the occurrence of a second clinical episode establishes the diagnosis of MS.

The nature of multiple sclerosis

Multiple sclerosis (MS) has recently been classified according to its clinical course. Despite relapses and remissions, its course is invariably progressive, and the observed progression from the remitting-relapsing to the secondary progressive form represents the accumulation of permanent damage to the nervous system. Discussions of the nomenclatural position of Schilder’s, Marburg’s, and Baló’s diseases, ignore the fact that the unique, pathognomonic, sharp-edged plaque of MS, is also the pathologic end-result in the three variants. Devic’s disease or neuromyelitis optica (NMO) is quite different and with some exceptions, is a particular form of disseminated encephalomyelitis (DEM). There is no evidence that the ‘oriental form of MS’ is anything but NMO. The suggestion that MS and DEM are variants of the same condition is contradicted by the fact that the pathological characteristics of the two are quite different. While it is probable that the two share aspects of pathogenesis, the patients differ because of their genetic endowment. This was dramatically demonstrated in a group of Japanese patients who died after anti-rabies vaccination and were found to have the typical sharp-edged lesions of MS. The genetic determinant was also crucial in the marmoset in which EAE uniquely resulted in a chronic relapsing-remitting (RR) disease characterized by the classic sharp-edged lesions of MS. The question ‘ADEM: distinct disease or part of the MS spectrum?’ can be answered with a resounding no. A new classification is proposed separating the different forms of MS from the various types of DEM.

Cerebral demyelination in Wegener’s granulomatosis

A 38-year-old woman with a history of a granulomatous lesion of the nose, developed blurred vision, ataxic gait, and spastic tetraparesis. The presence of demyelination on the brain MRI led to the diagnosis of cerebral demyelination associated with Wegener’s granulomatosis. Pulse cyclophosphamide administration resulted in some clinical of improvement of her condition. Demyelinating lesions seen in Wegener’s have been ascribed to multiple sclerosis, but in this case, they are much more reminiscent of disseminated encephalomyelitis (DEM). The immunological challenge of the underlying disease, may, in the genetically susceptible person, presumably trigger the appearance of MS lesions. Wegener’s granulomatosis must be considered in the differential diagnosis of MS.

Nuclear magnetic resonance tomographic appearance of disseminated encephalomyelitis in relation to clinical diagnosis

The MRI findings in 149 patients with a clinical diagnosis of disseminated encephalomyelitis (D.E.) were related to the diagnostic criteria of McAlpine (definite, probable, possible). The most common pattern in all three groups was a mixed peri- and para-ventricular distribution of foci. The findings in 'possible' D.E., compared with 'definite' D.E., showed fewer confluent lesions, but were characterised by peri- and para-ventricular as well as solitary foci. The results of the present study permit better classification and evaluation of the MRI findings if the clinical diagnosis of D.E. is only suspected (probable or possible).