Diagnosis Of Pediatric Multiple Sclerosis Research Articles

Neutrophil/lymphocyte and monocyte/lymphocyte indexes as potential predictors of relapse at 1 year after diagnosis of pediatric multiple sclerosis: a single-center, exploratory and proof-of-concept study.

Early identification of patients with a more unfavorable outcome in Multiple Sclerosis (MS) is crucial to optimize individualized treatment. Neutrophil-lymphocyte index (NLI) and monocyte-lymphocyte index (MLI) have been considered as potential biomarkers for disease prognosis. Our study aims to investigate the usefulness of NLI and MLI as predictors of relapse, disability progression, and lesion accumulation on magnetic resonance imaging (MRI) 1 year after diagnosis and treatment initiation, in pediatric-onset MS. A retrospective single-center study was conducted, including patients with diagnosis of MS established in pediatric age (<18 years old), at least 1-year of follow-up, and a complete blood count (CBC) performed at diagnosis. We collected the nearest-to-diagnosis NLI and MLI, as well as clinical and imaging variables, at diagnosis and 12 months later. Our cohort was further dichotomized into two groups, based on the presence of relapses. Statistical significance was considered for p < 0.05. Eighteen patients (n = 18) were included. The relapsing group had higher mean, minimum, and maximum values for both NLI (5.17 ± 5.85, range: 1.57-11.92) and MLI (0.35 ± 0.22, range: 0.19-0.59), compared to the non-relapsing group (2.19 ± 1.63, range: 1.12-7.32 for NLI, and 0.24 ± 0.09, range: 0.14-0.44 for MLI). A higher percentage of patients in the relapsing group had increased NLI (>1.89, 66.7%) and MLI (>0.21, 66.7%) values than those in the non-relapsing group (46.7%). Patients who presented new T2-hyperintense lesions on MRI after 1 year of follow-up also had higher mean, minimum, and maximum values of both biomarkers. Patients who did not achieve No Evidence of Disease Activity-3 (NEDA-3) state exhibited higher values for both ratios. However, in our sample, no statistically significant correlations were found between MLI and NLI values and the clinical and imaging variables considered. The ease of obtaining NLI and MLI from routine blood tests renders them useful biomarkers as a screening tool in longitudinal follow-up. Our study was based on a very small sample size, but it allowed us to verify the feasibility of the protocol used. It is intended to involve other centers in the next phase of this work, testing the possible usefulness of the indices under analysis on a larger sample.

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Sjögren syndrome in childhood mimicking pediatric multiple sclerosis

Abstract The differential diagnosis of pediatric multiple sclerosis (MS) presents a wide spectrum of diseases. Sjögren syndrome (SS) is also a rare cause of this disease. Neurological involvement in SS ranges from peripheral neuropathies to the central nervous system (CNS). We report the case of a 5-year-old boy with a possible diagnosis with SS based on positive minor salivary gland biopsy findings and positive anti-smooth muscle antibodies, also fulfilling the 2017 McDonald criteria. If a patient is younger and meets the MS criteria clinically and radiologically, it is suggested to carefully examine the CNS demyelination in a patient for autoimmune diseases, particularly SS.

A combination of Q-TOF LC/MS and LC-MS/MS based metabolomics in pediatric-onset multiple sclerosis demonstrates potential biomarkers for unclassified patients.

Metabolomics has the potential to provide putative biomarkers and insights into the pathophysiology and diagnosis of pediatric multiple sclerosis (pMS), which is an inflammatory demyelinating disorder of the central nervous system with a broad spectrum of clinical manifestations. In this study, we aimed to investigate serum metabolomics in pMS to help elucidate the pathophysiology of MS. An untargeted approach was applied using the quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS) method to study plasma metabolites in patients with pMS (n = 33), patients with unclassified central nervous system demyelinating diseases (n = 6), and age-matched healthy control subjects (n = 40). The patient and control groups were compared for metabolites and the normalized peak areas differed statistically (p < 0.05), showing at least a 1.25-fold change between groups. Bioinformatic tools combined with a clinical perspective were employed for the identification of the putative metabolites. In addition to the untargeted metabolomics approach, targeted LC-MS/MS metabolite analysis was employed to compare the pMS group with the control group. Significant differences between the patient and control groups were noted for tyramine, 4-hydroxyphenylacetaldehyde, sphingosine/3-dehydrosphinganine, prostaglandins/thromboxane A2, 20-hydroxy-leukotriene E4, 3α,7α,12α-trihydroxy-5β-cholestan26-al/calcitriol, pantetheine, ketoleucine/3-methyl-2-oxovaleric acid, L-arginine/D-arginine, coproporphyrinogen III, (S)-reticuline, carnosine, cytidine, and phosphoribosyl pyrophosphate. Additional tests for sphingosine 1-phosphate, sphingophosphocholines, ceramides, oxysterols, and calcitriol levels yielded significant metabolomic differences for the pMS group compared to the control group. The metabolomic data of 3/6 patients with unclassified demyelinating disorders matched the pMS group; their follow-up verified the diagnosis of pMS. In general, plasma metabolites related to sphingolipid metabolism, myelin products, inflammatory pathways, mitochondrial dysfunction, and oxidative stress were found to be altered in cases of pMS. The method applied in this study, combining untargeted analysis with a targeted approach, can be applied to larger series of cases of pMS and other demyelinating disorders for further validation.

Utility of paramagnetic rim lesions on 1.5-T susceptibility phase imaging for the diagnosis of pediatric multiple sclerosis.

Studies have suggested that paramagnetic rim lesions on 7-tesla (T) and 3-T susceptibility-based brain MRI are specific features of multiple sclerosis (MS) lesions in adults. The aim of this study was to investigate whether the presence of paramagnetic rim lesions on 1.5-T phase images can help discriminate pediatric patients with MS from those with other demyelinating diseases. In this retrospective study we reviewed brain MRIs performed on 1.5-T scanners that included susceptibility-weighted imaging (SWI) sequences with phase images in children younger than 18years diagnosed with MS and other acquired demyelinating syndromes. In each case, five white matter lesions were selected using T2/fluid-attenuated inversion recovery images for further paramagnetic rim evaluation on SWI. Two researchers performed independent assessments of the presence of paramagnetic rim lesions. Discrepancies between them were settled by consensus, with input from a senior neuroradiologist. We included 13 children diagnosed with MS and 16 children diagnosed with non-MS demyelinating diseases and analyzed a total of 132 focal white matter lesions. Seventy-one percent of the lesions in the MS group had paramagnetic rims, while none of the lesions in the non-MS group had rims. All but one of the children with MS had at least one lesion with a paramagnetic rim. The presence of one lesion with a paramagnetic rim on 1.5-T phase-contrast images resulted in 70% sensitivity and 100% specificity for MS. Paramagnetic rim lesions detected on 1.5-T phase-contrast MR images can help discriminate MS from other acquired demyelinating syndromes in the pediatric population.

Differential Diagnosis of Pediatric Multiple Sclerosis.

The differential diagnosis of pediatric multiple sclerosis (MS) can be broad and pose diagnostic challenges, particularly at initial presentation. Among demyelinating entities, neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibodies (MOG-ab) associated disorders, and acute disseminated encephalomyelitis (ADEM) are now well-known as unique disease processes and yet continue to overlap with MS in regards to clinical presentation and imaging. In non-inflammatory entities, such as metabolic disorders and leukodystrophies, an erroneous diagnosis of MS can be made even while applying appropriate diagnostic criteria. Knowing the epidemiology, typical clinical presentation, diagnostic criteria, and ancillary test results in each disease, can aid in making the correct diagnosis by contrasting these features with those of pediatric MS. Determining the correct diagnosis early, allows for efficient and effective treatment as well as appropriate prognostication.

Insights and Recommendations From Parents Receiving a Diagnosis of Pediatric Multiple Sclerosis for Their Child.

Forty-two parents of 41 children reported on their experiences receiving a diagnosis of pediatric-onset multiple sclerosis for their child through semistructured phone interviews. Time to diagnosis ranged from 8 hours to 16 years, with the mean age at diagnosis of 13.7 years. The most common initial symptoms included visual disturbances and numbness. The mean number of medical visits to receive a diagnosis was 3.6. Parents reported feeling frustrated and overwhelmed during the diagnosis process, as well as shocked when told their child had multiple sclerosis. Parents emphasized the need for more awareness of pediatric-onset multiple sclerosis. Numerous parents reported encountering physicians who believed multiple sclerosis did not occur in childhood, contributing to a longer time to diagnosis. Parents preferred physicians first share the diagnosis with the parents without the child present. Finally, parents appreciated when physicians provided a variety of resources to help them cope with the diagnosis.

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

Treatment of pediatric multiple sclerosis.

The past 10years have borne witness to increased recognition and diagnosis of pediatric multiple sclerosis (MS). Additionally, during this time period, the number of treatment options available for MS patients has increased significantly, as has the number of studies evaluating the use of these therapies in children. Though the U.S. Food and Drug Administration has not formally approved any of these therapies for use in pediatric MS, a number of injectable, oral, and intravenous treatments are currently being used off-label in these children. Disease modifying therapy should be initiated promptly following a diagnosis of MS. The patient and family should be engaged in the choice of therapy as this is likely to promote adherence. First-line options include any of the injectable therapies (glatiramer acetate, interferon beta), which have roughly similar efficacy (approximately 30% reduction of clinical relapses). If a patient has breakthrough disease or persistent, unmanageable side effects, transition to a different first-line therapy or escalation to a second-line therapy, such as natalizumab, should be considered. Though the efficacy of second-line agents is higher, the potential risk of serious adverse effects also increases. New therapies, including oral agents, are now being rigorously studied with pediatric clinical trials and may provide safe alternatives for patients that are either unresponsive or intolerant to currently available medications. When necessary, acute exacerbations can be treated with corticosteroids. Intravenous methylprednisolone at a dosage of 30mg/kg/day (maximum dose 1000 mg/day) for 3-5 days is recommended with severe attacks. If patients are unresponsive to corticosteroids, treatment with either intravenous immunoglobulin or plasma exchange may be required. Fatigue, spasticity, and pain can also occur in pediatric patients with MS. Medications are needed if symptoms are severe and impact quality of life.

Changes in Gross Grasp Strength and Fine Motor Skills in Adolescents with Pediatric Multiple Sclerosis

ABSTRACTThis study examined the gross grasp strength and fine motor dexterity of adolescents, who are diagnosed with multiple sclerosis (MS). A total sample size of 72 participants between the ages of 13 to 17 was studied. Thirty six with a diagnosis of pediatric relapse remitting MS and 36 matched control participants were selected from various local youth groups. Data on hand strength and dexterity was collected using a dynamometer, nine hole peg board and Purdue pegboard on both groups. Utilizing ANCOVA to describe the differences across the two groups by diagnosis, controlling for age and gender, it was found that the MS group demonstrated significantly decreased dexterity when compared to age and gender matched controls. There was no significant difference in gross grasp strength by diagnostic group. This preliminary study showed that children with a diagnosis of pediatric MS may have differences in fine motor dexterity, but not gross grasp strength from their peers who do not have the diagnosis. Further study is indicated to examine this phenomenon.

Mcdonald Diagnostic Criteria for Pediatric MS

Researchers at the Hospital for Sick Children, University of Toronto and other centers in Canada used serial clinical and MRI examinations performed over a minimum of 24 months to retrospectively evaluate the 2010 and 2005 McDonald criteria for the diagnosis of pediatric multiple sclerosis (MS).

Protein expression profiles in pediatric multiple sclerosis: potential biomarkers

The diagnosis of pediatric multiple sclerosis (MS) is challenging due to its low frequency and the overlap with other acquired childhood demyelinating disorders of the central nervous system. To identify potential protein biomarkers which could facilitate the diagnosis, we used two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry to identify proteins associated with pediatric MS. Plasma samples from nine children with MS and nine healthy subjects, matched in aggregate by age and gender, were analyzed for differences in their patterns of protein expression. We found 12 proteins that were significantly up regulated in the pediatric MS group: alpha-1-acid-glycoprotein 1, alpha-1-B-glycoprotein, transthyretin, apoliprotein-C-III, serum amyloid P component, complement factor-I, clusterin, gelsolin, hemopexin, kininogen-1, hCG1993037-isoform, and vitamin D-binding protein. These results show that 2-DE in combination with mass spectrometry is a highly sensitive technique for the identification of blood-based biomarkers. This proteomic approach could lead to a new panel of diagnostic and prognostic markers in pediatric MS.

MRI in the diagnosis of pediatric multiple sclerosis

MRI diagnostic criteria have not yet been adopted for pediatric multiple sclerosis (MS). MRI plays a pivotal role in supporting the diagnosis of MS in adults. We sought to quantitatively define the MRI features of pediatric MS, to determine features that distinguish MS from nondemyelinating relapsing childhood neurologic disorders, and to propose MRI criteria for lesion dissemination in space in children with MS. A retrospective analysis of MRI scans from 38 children with clinically definite MS and 45 children with nondemyelinating diseases with relapsing neurologic deficits (migraine, systemic lupus erythematosus) was performed. For each scan, T2/FLAIR hyperintense lesions were quantified and categorized according to location and size. Mean lesion counts in specific locations were compared between groups to derive diagnostic criteria. Validation of the proposed criteria was performed using MRI scans from a second independent MS cohort (n = 21). MRI lesion location and size categories differed between children with MS and nondemyelinating controls with a medium to large effect size for most variables. The presence of at least two of the following-five or more lesions, two or more periventricular lesions, or one brainstem lesion-distinguished MS from other nondemyelinating disease controls with 85% sensitivity and 98% specificity. We propose modifications to the currently established McDonald MRI criteria for lesion dissemination in space that will enhance the diagnostic accuracy of these criteria for multiple sclerosis in children.