Word-Finding Difficulties as a Prominent Early Finding in a Later Diagnosis of Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common neuropsychological disorder primarily diagnosed in childhood. Early intervention was found to significantly improve developmental outcomes, implicating on the role of early identification of ADHD markers. In the current study, we explored the developmental history of children referred to neurological assessment to identify early ADHD predictors. METHODS: A total of 92 children and adolescents (41 females) recruited at a pediatric neurology clinic, with suspected ADHD (n = 39) or other neurological difficulties (n = 53) such as headaches, seizures, tic disorders, orthostatic hypotension, postischemic stroke, intermittent pain, and vasovagal syncope. Developmental history information was obtained from caregivers, and evaluation for possible ADHD was performed. Developmental details were compared between children with and without current ADHD diagnosis. RESULTS: Word-finding difficulties (WFDs) in preschool age was reported in 30.4% of the sample. Among children diagnosed with ADHD, 43% had WFDs history, compared with only 5% in children without ADHD. Among children with WFDs history, 93% were later diagnosed with ADHD compared with 42% in children without WFDs history. The relationship between WFDs and ADHD was significant (chi-square test [1, N = 92] = 20.478, p < 0.0001), and a logistic regression model demonstrated that asides from a family history of ADHD, the strongest predictor for ADHD in school age children was a history of WFDs. CONCLUSION: Preliminary evidence supports a predictive link between preschool WFDs and later ADHD diagnosis, highlighting the importance of early WFDs clinical attention.

Body mass index and migraine in adolescence: A nationwide study.

BACKGROUND: The association between body mass index (BMI) and migraine in adults has been well established. However, studies in children and adolescents are inconclusive. We aimed to study the association between BMI and migraine using a national dataset that comprises the electronic medical records of more than two million adolescents. METHODS: This study included all Israeli adolescents (57.7% males, 42.3% females; mean age 17 years) who were medically assessed before mandatory military service during 1990-2020. As part of the pre-recruitment medical assessment, all the adolescents were screened for migraine and their height and weight were measured. Diagnoses of migraine were confirmed by board-certified neurologists. Prevalences and odds ratios (ORs) for migraine were computed across BMI subgroups. Spline models were applied. RESULTS: A total of 2,094,862 adolescents were included, of whom 57,385 (2.8%) had active migraine. Among males, the adjusted ORs for migraine were 1.11 (95% confidence interval, 1.06-1.16), 1.13 (1.08-1.17), and 1.24 (1.19-1.30), for the underweight, overweight, and obesity subgroups, respectively, compared to the reference group of low-normal BMI (5th-49th percentile). Among females, the respective adjusted ORs were 1.12 (1.05-1.19), 1.23 (1.19-1.28), and 1.38 (1.31-1.46). Results persisted in sensitivity analyses accounting for other medical and psychiatric comorbidities and parental history of migraine. Spline models demonstrated a J-shaped relation between BMI and migraine. CONCLUSIONS: Both adolescent obesity and underweight were associated with migraine in a sex-dependent manner. This association peaked in female adolescents with overweight and obesity.

Alemtuzumab mediates the CD39+ T-regulatory cell response via CD23+ macrophages.

Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T-regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may be indirectly affected by monocyte-derived cells, which are resistant to ALM cytotoxicity. We aimed to examine whether ALM modulates monocytes and whether the crosstalk between monocytes and lymphocytes previously exposed to ALM would result in anti-inflammatory effects. The CD14+ monocytes of 10 healthy controls and 10 MS (treatment naive) patients were isolated from peripheral blood mononuclear cells (PBMCs), exposed to ALM and reintroduced to PBMCs depleted of CD14+ cells. The macrophage profile was assessed and T-cell markers were measured. ALM promoted M2 anti-inflammatory phenotype as noted by an increased percentage in the populations of CD23+ , CD83+ and CD163+ cells. The CD23+ cells were the most upregulated (7-fold, P = 0.0002), and the observed effect was higher in patients with MS than in healthy subjects. ALM-exposed macrophages increased the proportion of T-regulatory cells, without affecting the proportion of T-effector cells. Neutralizing the CD23+ monocytes with antibodies reversed the effect specifically on the CD4+ CD39+ T-regulatory cell subpopulation but not on the CD4+ CD25hi CD127lo FOXP3+ subpopulation. ALM induces the conversion of monocytes into anti-inflammatory macrophages, which in turn promotes T-regulatory cell enhancement, in a CD23-dependent manner. These findings suggest that the mechanism of action of ALM is relevant to aspects of MS pathogenesis.

Search for new biomarkers of pediatric multiple sclerosis: application of immunoglobulin free light chain analysis.

BACKGROUND: Identifying new biomarkers is needed to overcome the diagnostic difficulties of pediatric multiple sclerosis (MS). Recently, we developed a new technique including CSF analysis of free light chain (FLC) monomers and dimers, which can improve diagnosis of adult MS. The present study has been designed to evaluate the utility of our technique for MS diagnosis in children. METHODS: Patients with MS (n=21) and non-MS demyelinating or inflammatory neurological disorders (n=35) participated in the study. MS diagnosis was based on clinical and magnetic resonance imaging (MRI) findings. Western blot analysis was applied to examine FLC in the patients' CSF and serum. FLC indices for FLC monomer and dimer levels and κ/λ ratios were estimated. The samples were also analyzed by oligoclonality test. RESULTS: The study revealed abnormally elevated levels of κ-FLC monomers and dimers in the CSF of 10 MS patients ("κ-type MS"). Increased amounts of λ dimers were found in six MS cases ("λ-type MS"), while high levels of both κ and λ FLC ("mixed type MS") were documented in three MS cases. MRI and clinical assessment showed a more aggressive disease form for the "mixed" and "λ-type" cases. Our method demonstrated higher sensitivity (90.5%) and specificity (91.4%) for discrimination between MS and non-MS patients, as compared to oligoclonality test (81% and 65.7%, respectively). CONCLUSIONS: The proposed method may significantly contribute to diagnosis and prognosis of pediatric MS.

Cytokine Production by Mononuclear Cells from Patients with Familial Infantile Bilateral Striatal Necrosis.

Prompted by findings suggesting immune instability in infantile bilateral striatal necrosis (IBSN), we evaluated levels of proinflammatory (tumor necrosis factor α, interleukin [IL]-1ß, IL-6, interferon [IFN]γ) and anti-inflammatory (IL-10 and IL-1ra) cytokines produced by peripheral blood mononuclear cells (PBMC) from 6 children with IBSN and 11 age-matched controls. Compared to controls, non-stimulated PBMC from the IBSN group produced a significantly lower level of IL-1ra (by 38%; p < 0.001) and significantly lower levels of TNFα, IL-1ß, and IFNγ (by 36% [p < 0.001], 25% [p = 0.06], and 32% [p < 0.02]) under PBMC stimulation. The severe cachexia manifesting shortly after IBSN onset may impair the immunological state, placing patients at risk of death from hyperpyrexia and sepsis.

Epilepsy and behavioral changes, type 1 diabetes mellitus and a high titer of glutamic acid decarboxylase antibodies.

Autoantibodies to the 65 kDa isoform of glutamate acid decarboxylase (GAD65Ab) are associated with a range of clinical disorders, including type 1 diabetes (T1D) and stiff-person syndrome (SPS). In this article we describe a young girl who was diagnosed with T1D at the end of her first year of life and developed drug-resistant epilepsy 18 months later, followed by behavioral disturbances. She was admitted to our center at the age of 5 yr, at which time high GAD65Ab titers were detected in the patient's serum and cerebrospinal fluid (CSF). The titer remained elevated during 19 months of follow-up. Furthermore, GAD65Ab in both serum and CSF showed epitope binding characteristics similar to those observed for GAD65Ab in SPS patients, and GAD65Ab in the serum reduced GAD65 enzyme activity. Our results suggest an association between high GAD65Ab titers and epilepsy in children with T1D. Careful titration and characterization of GAD65Ab regarding inhibition of enzyme activity and epitope specificity may be helpful in identifying T1D patients at risk for neurological complications.

Well-being among parents of youth with multiple sclerosis: a preliminary longitudinal study.

Background: In 2021, the annual rate of pediatric-onset multiple sclerosis (POMS) in Israel among children was 1.5, and 4.5% among youth aged 14-18, out of a total of 5,000 multiple sclerosis cases nationwide. Children diagnosed with POMS often display various deficiencies across psychological, cognitive, sensory, and physical areas. As such, POMS poses significant challenges for parents' well-being, with heightened emotional, financial, and physical strains linked to both the immediate and long-term care requirements of their children. In this preliminary study, we examined changes over three time-points in two measures of well-being: satisfaction with life and psychological distress. In addition, the role of perceived social support (PSS) and coping flexibility was examined through a multilevel causal mediation model which suggested that PSS 1 month post-diagnosis would predict coping flexibility at 6 months post-diagnosis, which in turn would predict parents' life satisfaction and psychological distress at 12 months post-diagnosis. Methods: The research was conducted at a tertiary university-affiliated children's hospital in central Israel. Preliminary data were obtained from 36 parents at three times-points. Participants provided demographic information and filled out the following standardized self-report questionnaires: the Diener's Satisfaction with Life Scale, Kessler's inventory for measuring psychological distress (K6), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Perceived Ability to Cope with Trauma Scale (PACT) for measuring coping flexibility. Results: Over time (12 months), parents reported stable levels of PSS, coping flexibility, satisfaction with life, and psychological distress. In addition, mothers reported significantly greater PSS from friends than did fathers. Regarding the causal mediation model, greater PSS from friends at T1 was significantly associated with an increase in coping flexibility from T1 to T2. In turn, an increase in coping flexibility was associated with a decrease in psychological distress from T1 to T3 (after controlling for PSS). Yet the causal mediation path via coping flexibility to satisfaction with life was not significant. Conclusion: This preliminary study emphasizes the important role of both PSS and coping flexibility for the well-being of parents whose children are affected by POMS, a subject that merits heightened consideration among healthcare professionals dealing with long-term chronic diseases.

Steps Toward Decreasing Maternal Alcohol Consumption in Israel: Nationwide Trends During a Decade.

OBJECTIVES: Prenatal alcohol exposure poses a substantial risk to fetal development. Efforts were made in 2011-2020 to increase public awareness of and prevent alcohol consumption during pregnancy. We conducted a cross-sectional survey in Israel of pregnant women's alcohol consumption from January 2021 through June 2023 and compared our results with the results of a survey conducted during 2009-2010 to assess changes over time. METHODS: We conducted cross-sectional surveys at 3 public hospitals in central and northern Israel. Surveyors visited hospitals twice weekly and used a questionnaire consistent with one used in 2009-2010 that focused on alcohol consumption 3 months before pregnancy and during pregnancy. We conducted a stratified analysis of the prevalence of alcohol consumption during pregnancy by demographic characteristics. We also used a multivariable logistic regression model to examine variables associated with receiving guidance on alcohol consumption during pregnancy. RESULTS: Of 1915 women in the 2021-2023 survey (mean [SD] age, 30.8 [5.6] y), 1204 (62.9%) reported never consuming alcohol before pregnancy and 1708 (89.2%) reported no alcohol consumption during pregnancy. During pregnancy, 157 (8.2%) women reported consuming alcohol weekly or less, 12 (0.6%) more frequently, and 52 (2.7%) binge drinking. We found a significant decrease in alcohol consumption during pregnancy in 2021-2023 as compared with 2009-2010 (odds ratio, 0.68; 95% CI, 0.52-0.88; P = .03). Predictors of alcohol consumption during pregnancy included alcohol consumption before pregnancy, parity, and smoking. Significantly more women in the 2021-2023 sample (n = 569; 29.7%) than in the 2009-2010 sample received guidance on alcohol consumption during pregnancy (P < .001). CONCLUSIONS: Educational efforts should continue to increase awareness of the risks of prenatal alcohol exposure in the general population and among health professionals.

The effect of COVID-19 vaccination on multiple sclerosis activity as reflected by MRI.

INTRODUCTION: Examining the safety of theBNT162b2 mRNA vaccine in multiple sclerosis (MS) patients remains inconclusive, particularly regarding the potential for disease exacerbations. This study aims to assess the effects of BNT162b2 COVID-19 vaccination on disease activity in MS patients through sequential MRI imaging. METHODS: A retrospective study of 84 MS patients from five Israeli hospitals was conducted. MS lesion load was determined from three brain MRI scans, one postvaccination and two prevaccination scans. A post hoc analysis compared subgroups featuring vaccinated and unvaccinated patients respectively, with early onset MS. RESULTS: The cohort included 70 women with early onset (mean age 16.4 ± 0.8 years) and adult onset (mean age 34.9 ± 1.1 years) MS. Among the early onset group, vaccinated patients showed an increased risk of new lesions (p = .00026), while there was no increased risk among adult-onset patients. Additionally, a comparison between early onset vaccinated and nonvaccinated groups revealed a higher risk of increased lesions in the vaccinated group (p = .024). DISCUSSION: Overall, the study suggests that the BNT162b2 vaccine is generally safe in MS patients, with no association found between vaccination and new lesions in most patients. However, close MRI follow-up is recommended for early-onset MS cases to monitor lesion development.

Cognitive impairments in autoimmune encephalitis: the role of autoimmune antibodies and oligoclonal bands.

Introduction: The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. Methods: We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher's exact test with Benjamini-Hochberg correction. Results: Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Conclusions: Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects.

Disordered sleep in pediatric patients with attention deficit hyperactivity disorder: an overview.

There is a well-established correlation between sleep disturbances and attention deficit hyperactivity disorder (ADHD). A large number of pediatric patients diagnosed with ADHD have sleep problems, while patients with sleep disturbances often display behavioral patterns that resemble some features of ADHD. Despite these observations, the relationship between sleep problems and ADHD is not yet fully understood. It is often difficult to pinpoint which of the disorders is the primary and which a byproduct of the other. A complicating factor is that stimulant medication such as methylphenidate, a drug of choice for ADHD, may adversely affect sleep quality in ADHD patients. However, there have also been reports that it may actually improve sleep quality. This review examines the latest trends in the contemporary literature on this clinical dilemma.

[Narcolepsy as an autoimmune disease].

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and irresistible sleep attacks that occur during the activities of daily living. Falling asleep in the middle of essential activities such as driving or crossing the street may lead to life-threatening situations. Narcolepsy is estimated to affect 0.002% of the Israeli population. By using animal models, human autopsies and brain biopsies, it has recently been shown that the destruction of the orexin-secreting neurons underlies the pathogenicity of this disease. Orexin is a neurotransmitter involved in the sleep arousal cycle and also in the development of hunger sensations. Based on circumstantial evidence, it is estimated that the autoimmune system is responsible for the destruction of the orexin-secreting neurons. There are several findings in the literature that might connect the autoimmunity with the narcolepsy existence. For instance: narcolepsy is associated with high frequency of specific HLA system alleles, especially DQB1*0602. Furthermore, polymorphism in the alpha chain of the T cell receptors was found among narcolepsy patients. A more direct connection is the discovery of the Trib--an autoantigen. This protein is presented by orexin-secreting neurons and was recently found in narcoleptic patients exclusively, and not in the healthy control group. Nevertheless, there is still no agreement within the scientific community since a direct link between the autoimmune mechanism and narcolepsy has not yet been proved. Several trials using immune modulator therapy did not show any significant improvement.

Dual positivity for anti-MOG and oligoclonal bands: Unveiling unique clinical profiles and implications.

BACKGROUND: Distinguishing between MOG-associated disease (MOGAD) and multiple sclerosis (MS) presents a considerable challenge, as there are instances of overlapping clinical presentations. This complexity is further magnified in cases where patients concurrently exhibit both anti-myelin oligodendrocyte glycoprotein (anti-MOG) positivity and detectable oligoclonal bands (OCBs) This retrospective study investigates the clinical and imaging attributes of dual-positive patients, those with both anti-MOG positivity and OCBs, The study aims to show potential areas of overlap between multiple sclerosis (MS) and MOGAD. METHODS: Utilizing data gathered from three medical centers, we evaluated a cohort of 45 patients, stratifying them into two groups: those exclusively positive for anti-MOG antibodies and those displaying dual positivity. Our analysis encompassed a wide range of clinical and imaging parameters. The statistical techniques employed comprised Fisher's Exact Test along with Benjamini-Hochberg correction to ensure robustness of the findings. RESULTS: The study involved 45 patients with anti-MOG antibodies; 30 exhibited isolated anti-MOG positivity without OCBs, while 15 were dual-positive. The first group's average age was 10±7 years, compared to 28±17 years in the double-positive group (p = 0.001). CSF analysis showed no significant differences in pleocytosis, protein levels, or opening pressure between the groups. In the exclusive anti-MOG positivity cohort, 9 out of 15 patients received IVIG treatment; a larger subgroup with dual positivity chose anti-CD20 treatment. Notably, papilledema incidence was higher in the single-positive group (p = 0.014). Optic nerve enhancement (p = 0.0038) and nerve thickening (p = 0.0017) were markedly elevated in the single-positive population, with a trend towards pre-chiasmatic lesions (p = 0.06). Double-positive cases exhibited more polyfocal presentation (p = 0.013) and higher attacks per case (p = 0.002, HR=10.2, 95 % CI: 2.19 to 49.23). The double-positive group had more brain lesions (p = 0.0063) but no significant distinctions in other aspects. CONCLUSION: The results emphasize the challenges inherent in differentiating between MS and a more MOGAD. While the data suggest two plausible scenarios-either falling within the spectrum of MS or representing an intensified MOGAD-we recognize the need for stronger evidence to definitively classify these instances. This study underscores the imperative for thorough investigations to ascertain whether these cases align with the MS spectrum or denote an inflammatory variant of MOGAD.

The contribution of the Neurobehavioral Screening Tool to identifying fetal alcohol spectrum disorders in children at high risk of prenatal alcohol exposure and neurobehavioral deficits.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) describe various conditions resulting from prenatal alcohol exposure. The diagnosis of FASD can be challenging and complex. The Neurobehavioral Screening Tool (NST), derived from Achenbach's Child Behavior Checklist, has been suggested as a tool for identifying FASD. AIMS: To assess the external validity of the NST and to identify additional characteristics of FASD in a cohort of Israeli children and young adults referred to a neurology and child developmental clinic at a tertiary pediatric medical center in Israel. STUDY DESIGN: An observational study based on medical records. SUBJECTS: 151 children and young adults, of whom 40 were diagnosed with FASD according to updated clinical guidelines. OUTCOME MEASURES: NST results, as well as demographic and neurobehavioral variables, were compared between those who were and were not diagnosed with FASD. RESULTS: The NST demonstrated 72 % to 73 % sensitivity, and 34 % to 36 % specificity, in identifying FASD. Items 4 and 5 ('Lies or cheats', 'Lacks guilt after misbehaving') were the most predictive items in the NST. Other variables that were characteristic of the FASD group included: emotional regulation difficulties (p value <0.01), being born and adopted in Israel (vs. other countries) (p value <0.01) and younger age at the first visit to the clinic (p value <0.01). CONCLUSIONS: Our findings regarding the screening capabilities of the NST were less promising than those of most previous studies. Further research is needed to establish a valid neurobehavioral tool with the possible focus on antisocial behaviors and emotional regulation problems.

Personalized Disease Monitoring in Pediatric Onset Multiple Sclerosis Using the Saliva Free Light Chain Test.

Background: Development of new safe methods of monitoring disease activity in the pediatric onset multiple sclerosis (POMS) is a challenging task, especially when trying to refrain from frequent MRI usage. In our recent study, the saliva immunoglobulin free light chains (FLC) were suggested as biomarkers to discriminate between remission and active MS in adults. Objectives: To assess utility of saliva FLC measurements for monitoring disease activity in POMS. Methods: We used semiquantitative Western blot analysis to detect immunoreactive FLC monomers and dimers and to calculate the intensity of their bands. Statistical tests included Firth logistic regression analysis suitable for small sample sizes, and Spearman's non-parametric correlation. Results: In naive POMS patients, the saliva levels of FLC in relapse were significantly higher than those in remission. Significant correlation was found between FLC levels (monomers, dimers or both) and the load of enhanced lesions in MRI scans. FLC levels may be reduced under treatment, especially as result of corticosteroids therapy. Follow-up of individual patients showed the correspondence of changes in the FLC levels to MRI findings. Conclusions: Our results show the potential of the non-invasive saliva FLC test, as a new tool for monitoring the disease activity in POMS.

Age-Related Clinical Presentation of MOG-IgG Seropositivity in Israel.

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. Aim: To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. Methods: MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Results: Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1-66 years, with increased prevalence in children (19% compared to 6.7% in adults) (p < 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31-40 years (16.6%). Conclusions: MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.

Prognostic Parameters of Acute Transverse Myelitis in Children.

Acute transverse myelitis is a rare and disabling disorder. Data on the imaging features in children are sparse. The aim of this study was to describe the clinical and magnetic resonance imaging findings characteristic of pediatric idiopathic acute transverse myelitis and to identify those with prognostic value. The database of a tertiary pediatric medical center was retrospectively reviewed for patients aged less than 18 years who were diagnosed in 2002-2017 with acute transverse myelitis that was not associated with recurrence of a demyelinating autoimmune event. Data were collected on clinical, laboratory, and imaging findings and outcome. A total of 23 children (11 male, 12 female) met the study criteria. Mean age at disease onset was 10 years, and mean duration of follow-up was 6 years 10 months. Spinal cord and brain magnetic resonance imaging scans were performed on admission or shortly thereafter. The most common finding was cross-sectional involvement, in 16 patients (70%). The mean number of involved spinal segments was 8. The most frequently involved region was the thoracic spine, in 17 patients (74%). Clinical factors predicting good prognosis were cerebrospinal fluid pleocytosis, absence of tetraparesis, and prolonged time to nadir. In conclusion, most children with acute transverse myelitis appear to have a good outcome. Prompt diagnosis and treatment are important. Further research is needed in a larger sample to evaluate the predictive value of imaging features.

Saliva immunoglobulin free light chain analysis for monitoring disease activity and response to treatment in multiple sclerosis.

BACKGROUND: Immunoglobulin free light chains (FLC) have recently gained considerable interest as new promising intrathecal biomarkers of multiple sclerosis (MS). However, lumbar puncture is invasive and not practical for monitoring disease course. This study aimed to assess the utility of saliva FLC as a biomarker of disease activity and response to treatment in MS METHODS: Western blotting was used to study saliva FLC monomers and dimers. The intensity of immunoreactive FLC bands was quantified by electrophoresis analysis, and the obtained values were used as FLC indices to account for kappa and lambda FLC monomer and dimer levels. Firth's logistic regression analysis suitable to study small cohorts was applied to compare FLC levels between M.S. patients in relapse, MS patients in remission, and healthy controls. Association between FLC levels and clinical and radiological parameters was analyzed. RESULTS: 55 MS patients and 40 healthy controls were evaluated. Saliva FLC levels were significantly higher in relapse compared to remission. Logistic regression analysis employing a combination of FLC indices confirmed the significant difference between these two groups. The FLC levels were significantly reduced by treatment with corticosteroids. During remission, patients treated with disease-modifying therapies had lower levels of FLC compared to untreated patients. The increased FLC levels were associated with the presence of gadolinium-enhancing lesions, but not with MRI T2 lesion load and EDSS scores. During individual patient follow-up, the changes of the saliva FLC levels were in concordance with the disease activity status. CONCLUSIONS: Saliva FLC levels may be a useful biomarker for discriminating between stable remission and active disease. The developed test may serve as a new, non-invasive, and inexpensive tool for monitoring disease activity and response to treatment in MS.

Clinical Features at the Time of Diagnosis of Benign Epilepsy With Centrotemporal Spikes Do Not Predict Subsequent Seizures.

BACKGROUND: Benign epilepsy with centrotemporal spikes (BECTs) usually follows a self-limited course, with a single or few seizures. Assessing the likelihood of a second seizure after the first event may help establishing the need for antiepileptic drug therapy at the time of diagnosis. We aimed at identifying clinical and/or electrographic features that could predict the occurrence of a second seizure. METHODS: We reviewed the clinical and electroencephalographic (EEG) data of children diagnosed with BECTs between 2006 and 2012. Demographic, clinical, routine, and sleep-deprived EEG findings were analyzed. FINDINGS: Seventy-three patients were reviewed who had been followed for four to 10 years. Age at first seizure ranged between three and 16 years (median nine years). In 28 children the first seizure occurred after 10 years age. Ten children were aged three to six years. EEG data were available for 64 individuals. No specific clinical features or seizure semiology were predictive of a second seizure. Neither the type nor the location of interictal EEG discharges was indicative of a second seizure. Among children whose EEG records depicted sleep-related enhancement of interictal discharges, 58.8% sustained a second seizure. This finding did not reach statistical significance. Forty children sustained a second seizure, mostly within 12 months in 30 (P < 0.0001). Among these 30 children, the second event occurred after a median period of 156 days, compared with 654 days for cases with a second seizure after 12 months. CONCLUSIONS: Neither clinical features, seizure characteristics, nor routine EEG findings were effective in predicting the likelihood of a second seizure in children with BECTs.