The effects of online exercise training on physical functions and quality of life in patients with pediatric-onset multiple sclerosis.

BACKGROUND: Patients with pediatric-onset multiple sclerosis (PwPOMS) frequently experience motor, sensory, and cognitive problems. Although exercise is known to be effective in adult patients with MS, there are still no studies investigating the effectiveness of exercise in PwPOMS. To examine the effectiveness of online exercise training on physical activity, muscle strength, functionality, gait, fatigue, and quality of life in PwPOMS. METHODS: Twenty-one individuals were included and randomly divided into two groups. The online exercise training program (OETP) group received exercise training including aerobics, strengthening, and balance training for 8 weeks, and the control group received no intervention. Outcomes were assessed at baseline, 8 weeks, and 32 weeks. RESULTS: Significant improvements were recorded in physical activity, muscle strength, functionality, gait, fatigue, and quality of life in the OETP group after treatment (p<0.05). Between groups, the OETP group was superior to the control group in terms of physical activity, muscle strength, functionality, and quality of life (p<0.05). The OETP group remained superior to the control group in follow-up. CONCLUSION: OETP performed under the supervision of a physiotherapist is effective in PwPOMS. Even if these patients have no disabilities, it would be beneficial to refer them to rehabilitation from an early period.

The effects of nusinersen treatment on respiratory status of children with spinal muscular atrophy.

BACKGROUND: Respiratory involvement is the main factor predicting the prognosis of spinal muscular atrophy (SMA). Significant responses in motor functions have been demonstrated with nusinersen, but pulmonary outcomes are still varied. We aimed to explore the effects of nusinersen on the respiratory functions of patients with SMA. METHODS: Patients with SMA who were receiving regular nusinersen treatment in our tertiary care hospital were enrolled in this study. We evaluated the patients in terms of the necessity to ventilatory or nutritional support, presence of motor involvement and other comorbidities related with prognosis at three consecutive assessments. RESULTS: The study group consisted of 43 patients (18 type 1, 12 type 2, and 13 type 3) with SMA with a mean age of 27.8 months at diagnosis and 60.8 months at the beginning of nusinersen treatment. The respiratory function improvements were noted in six patients at third assessment. Early initiation of nusinersen was significantly correlated with reduced hospital admissions (P = 0.026). Nutritional support and weight gain were remarkable in the ventilatory-supported group. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were significantly higher in the non-tracheostomized group in patients with SMA type 1 (P < 0.005). CONCLUSIONS: We posit that nusinersen may change the natural prognosis of SMA and improve care of children with SMA. Following up children with SMA for longer periods under nusinersen may be beneficial for understanding the effects of treatment. Results of our study need to be supported by future long-term studies to reach a consensus on nusinersen, considering the overall genetic and environmental status as well as the cost-effectiveness of the treatment.

Six-Minute Walk Performance and Related Factors in Pediatric-Onset Multiple Sclerosis.

OBJECTIVE: To investigate functional exercise capacity and its relationship between physical activity levels, muscle strength, balance, fatigue, and quality of life in patients with pediatric-onset multiple sclerosis. METHODS: Fifteen patients with pediatric-onset multiple sclerosis were included. The 6-minute walk test was used to determine functional exercise capacity and walking distance. The Godin Leisure-Time Exercise Questionnaire and pedometer were used to evaluate physical activity, Timed-Up and Go for dynamic balance, isokinetic testing for lower extremity muscle strength, Fatigue Severity Scale for fatigue, and the Pediatric Quality of Life Inventory (PedsQL) for quality of life. RESULTS: The 6-minute walking distance was positively correlated with GLTEQ and the School-Work subgroup score of the PedsQL-Self-report, and negatively correlated with Timed-Up and Go and Fatigue Severity Scale. Dynamic balance, physical activity, and fatigue were significant predictors of 6-minute walking distance. CONCLUSIONS: Our results showed that 6-minute walk test is influenced by physical activity, dynamic balance, and fatigue, and related to quality of life in patients with pediatric-onset multiple sclerosis.

Acute flaccid myelitis outbreak through 2016-2018: A multicenter experience from Turkey.

AIM: We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. METHODS: The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. RESULTS: Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. CONCLUSION: The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.

The impact of SARS-CoV2 on the anxiety levels of subjects and on the anxiety and depression levels of their parents.

BACKGROUND: The Severe Acute Respiratory Syndrome-CoV2 outbreak was announced a pandemic by the World Health Organization on March 11th, 2020. Both the pandemic itself and the restrictions were thought to create some psychological problems especially in patients with chronic illnesses such as Multiple Sclerosis (MS). This study was conducted to evaluate the impact of SARS-CoV2 pandemic on daily lives of children with MS, and the anxiety status of these patients and anxiety - depression status of their parents. METHODS: This study was performed on a group of pediatric MS patients aged 8-18 years in Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, and Child Neurology Department. Thirty patients with MS and their 30 parents were enrolled to the study. The control group consisted of 49 healthy, age- and sex-matched children and their 49 parents. The patients (and their parents) were asked to complete a web-based survey evaluating access to health care and other changes in daily life between March 11th, 2020 and June 1st, 2020. The State-Trait Anxiety Inventory (STAI) [which is composed of two parts; S-anxiety (STAI-S) and T-anxiety (STAI-T)] was administrated to the patients and healthy controls and the results were compared between the two groups to assess their anxiety levels. The Hospital Anxiety and Depression Scale (HAD) [which is composed of two parts; HAD-anxiety (HAD-A) and HAD-depression (HAD-D)] was also given to all parents. The results of the HAD tests were compared between the two groups statistically. RESULTS: The results of the web-based survey showed that 4 of 9 (44.4%) patients, who had a regular workout program, left the program and 13 (43.3%) patients put on weight during the pandemic. Twenty-two patients (73.3%) could not get direct exposure to sunlight because of the curfew. Therefore, approximately half of the patients started to take vitamin D supplement. Most of the patients (80%) thought that they had higher risk and believed that they would have severe symptoms compared to healthy people. Twenty one (70%) patients disrupted their regular health checks and the most frequent causes were identified as closure of policlinics to routine patient care (33%) and concerns of getting SARS-CoV2 infection (26,6%). Two of 3 patients who had an MS attack did not go to the doctor during this period. The mean STAI-S scores in MS patients were significantly higher compared to the healthy controls (p=<0.001). The level of S-anxiety in all patients was higher compared to the cut off value.The mean HAD A score was found to be significantly higher in them compared to the parents of healthy individuals (p = 0.001). CONCLUSION: Our results showed that children with MS had negative changes in daily life and high anxiety levels during the pandemic. Since MS patients have also psychiatric comorbidities, they may need psychosocial support especially in this period. Besides, establishment of separate health centers to be used during pandemics for children with chronic illnesses such as MS may be recommended to facilitate access to health care.

Expanding Clinical Phenotype of TRAPPC12-Related Childhood Encephalopathy: Two Cases and Review of Literature.

Biallelic mutations in the TRAPPC12 gene are responsible for early-onset progressive encephalopathy with brain atrophy and spasticity (PEBAS). To date, three different allelic variants have been reported. Next-generation sequencing allowed discovery of unique alternations in this gene with different phenotypes. We report two patients carrying TRAPPC12 variants, one previously reported and one unknown mutation, with severe neurodevelopmental delay and brain atrophy. Standard clinical examination and cranial imaging studies were performed in these two unrelated patients. In addition, whole-exome sequencing was performed, followed by Sanger sequencing for verification. The first patient, a 2-year-old boy, was found to be homozygous for the previously reported c.1880C > T (p.Ala627Val) mutation. He presented with a phenotype including severe progressive cortical atrophy, moderate cerebellar atrophy, epilepsy, and microcephaly, very similar to the previously reported cases. The second case, a 9-year-old boy, carried a novel homozygous c.679T > G (p.Phe227Val) variant and presented with mild cortical atrophy, severe cerebellar atrophy, and neither clinically manifest epilepsy nor microcephaly, which were previously considered typical findings in PEBAS with TRAPPC12 mutations. Our findings suggest that clinical and brain imaging findings might be more variable than previously anticipated; however, a larger number of observations would benefit for broader phenotypic spectrum.

Acquired Chiari I Malformation Secondary to Spontaneous Intracranial Hypotension Syndrome and Persistent Hypoglycemia: A Case Report

Spontaneous intracranial hypotension (SIH) is a rare and potentially serious condition in childhood. Cerebrospinal fluid (CSF) volume depletion is thought to be the main causative feature for intracranial hypotension and results from a spontaneous CSF leak, often at the spine level. SIH is increasingly diagnosed in clinical practice, although it manifests a varied symptomatology. The downward displacement of the brain, sometimes mimicking a Chiari I malformation, has rarely been reported. We present a case of a SIH with Chiari I malformation accompanied by an unusual clinical presentation of persistent hypoglycemia.

Non epileptic paroxysmal events in childhood.

Non epileptic paroxysmal events are recurrent movement disorders with acute onset and ending, which may mimic epilepsy. The duration, place, timing of the attacks, and state of conciousness may confuse pediatricians about the diagnosis of epilepsy and non epileptic paroxysmal events. The key point in the diagnosis is taking an accurate and detailed history. Wrong diagnosis can give rise to anxiety of both the family and the child, interruptions in the child's education, limitations in career planning, and irreversible damages in the long term. The diagnosis can prevent unnecessary drug use and psychological damage. This review aims to discuss the clinical findings, treatment, and differential diagnoses of non epileptic paroxysmal events, and to increase awareness about non epileptic paroxysmal events among pediatricians.

Onychomadesis: A rare adverse effect in early-period valproic acid therapy.

Valproic acid is an effective, frequently used anticonvulsant drug. Typical adverse effects include weight gain, hair loss, and nausea. Hyperpigmentation, onycholysis, and onychomadesis are nail changes that can be seen after valproic acid use. Changes occur at the distal and proximal portions of the nail bed in onycholysis and onychomadesis, respectively. Onychomadesis is a very rare disease of childhood with the exception of systemic and genetic diseases. Here, we present a child aged 23 months, the youngest and the earliest isolated patient with onychomadesis, which occurred after valproic acid treatment and worried the family but resolved spontaneously. The improvement of this very rare adverse effect of antiepileptic drugs after cessation of valproic acid without treatment is emphasized.

Mixture models reveal multiple positional bias types in RNA-Seq data and lead to accurate transcript concentration estimates.

Accuracy of transcript quantification with RNA-Seq is negatively affected by positional fragment bias. This article introduces Mix2 (rd. "mixquare"), a transcript quantification method which uses a mixture of probability distributions to model and thereby neutralize the effects of positional fragment bias. The parameters of Mix2 are trained by Expectation Maximization resulting in simultaneous transcript abundance and bias estimates. We compare Mix2 to Cufflinks, RSEM, eXpress and PennSeq; state-of-the-art quantification methods implementing some form of bias correction. On four synthetic biases we show that the accuracy of Mix2 overall exceeds the accuracy of the other methods and that its bias estimates converge to the correct solution. We further evaluate Mix2 on real RNA-Seq data from the Microarray and Sequencing Quality Control (MAQC, SEQC) Consortia. On MAQC data, Mix2 achieves improved correlation to qPCR measurements with a relative increase in R2 between 4% and 50%. Mix2 also yields repeatable concentration estimates across technical replicates with a relative increase in R2 between 8% and 47% and reduced standard deviation across the full concentration range. We further observe more accurate detection of differential expression with a relative increase in true positives between 74% and 378% for 5% false positives. In addition, Mix2 reveals 5 dominant biases in MAQC data deviating from the common assumption of a uniform fragment distribution. On SEQC data, Mix2 yields higher consistency between measured and predicted concentration ratios. A relative error of 20% or less is obtained for 51% of transcripts by Mix2, 40% of transcripts by Cufflinks and RSEM and 30% by eXpress. Titration order consistency is correct for 47% of transcripts for Mix2, 41% for Cufflinks and RSEM and 34% for eXpress. We, further, observe improved repeatability across laboratory sites with a relative increase in R2 between 8% and 44% and reduced standard deviation.

Endocrinological Evaluations of a Neurofibromatosis Type 1 Cohort: Is it Necessary to Evaluate Autoimmune Thyroiditis in Neurofibromatosis Type 1?

BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder in which the coexistence of autoimmune thyroiditis and thyroid gland tumours has been reported previously. AIMS: To determine the thyroid function and autoimmune thyroid diseases in neurofibromatosis type 1 patients in order to identify the possible association between neurofibromatosis type 1 and thyroid diseases. STUDY DESIGN: Case-control study. METHODS: The study includes 78 consecutive patients diagnosed with neurofibromatosis type 1 between June 2010 and June 2014 and 50 healthy controls. Baseline demographic data were generated from patient examination record forms, including age, sex, height, and weight, as well as levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, anti-thyroid peroxidase and anti-thyroglobulin levels. RESULTS: Mean age, sex, and body mass index were similar in both groups (p>0.05). The mean levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were not statistically different between the neurofibromatosis type 1 and control groups. Similarly, no statistically significant difference was observed between the neurofibromatosis type 1 and control groups for anti-thyroid peroxidase and anti-thyroglobulin positivity (2.5% vs 0%, p>0.05). CONCLUSION: Screening for autoimmune thyroid disease and thyroid function seems to be unnecessary in patients with neurofibromatosis type 1.

The impact of epilepsy on preschool children and their families.

This study investigated the possible presence of sensory-motor developmental impairments in preschool children with epilepsy and explored epilepsy impact on their activities and quality of life and on the stress load of their family. Study participants were children aged 2-6years diagnosed with epilepsy without any other comorbidities (epi-only children). The instruments used for assessment included the Neurological, Sensory, Motor, Developmental Assessment (NSMDA) scale for sensory-motor development, the Impact of Childhood Neurologic Disability Scale (ICNDS), and the Impact of Pediatric Epilepsy Scale (IPES) for disease impact on disability and Quality of Life (QoL), as well as the Pediatric Outcomes Data Collection Instrument (PODCI) for functional health status, and the Parental Stress Scale (PSS) for the family stress load. Required data were obtained from direct testing or observation of children's activities and mother-supplied answers to questions. Eighty-two children were investigated. The NSMDA scores were in the normal development range 6-8. Significant moderate impact of the disease on disability and QoL was estimated with the ICNDS and IPES instruments. The PODCI scores were similar to healthy population levels except for the happiness dimension which was better for children with epilepsy. PSS were significantly above normal. The functional health and QoL of the children as well as their family stress were found to be positively correlated with increasing age. It is found that epilepsy does not degrade neuromotor development and functional health status of preschool epi-only children, though it has a significant impact on their neurological disability and QoL and the stress level of their families; this impact seems to decrease with age.

Relationship between the corpus callosum and neurocognitive disabilities in children with NF-1: diffusion tensor imaging features.

PURPOSE: Mild neurocognitive disabilities are commonly observed in children with neurofibromatosis type 1 (NF-1). Enlargement of the corpus callosum (CC) is one of the findings in NF-1, but the pathogenesis has not yet been clarified. In this study, we investigated whether diffusion tensor imaging (DTI) features of CC differed between children with NF-1 and healthy control subjects, and we tried to evaluate the association between the microstructural integrity of CC and neurocognitive disabilities, based on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values. MATERIALS AND METHODS: The study population consisted of 37 children with NF-1 and 31 healthy controls. Midsagittal CC surface area measurements were obtained from volumetric sagittal T1-weighted turbo spin echo images. FA and ADC values were obtained from the genu and splenium of CC. The results were compared to that of controls. The correlations between neurocognitive test results and measurements of ADC, FA, and surface areas of midsagittal CC in NF-1 patients were investigated. RESULTS: Total CC area in children with NF-1 was significantly larger than healthy controls. ADC values obtained from the genu of CC were significantly higher in NF-1 children. A negative correlation was observed between the ADC values of the genu of the CC and the arithmetic and digit span scores and between the FA values of the genu and coding scores in children with NF-1. CONCLUSION: The DTI changes in the genu of CC in children with NF-1 may indicate subtle structural damage, although conventional MRI is normal. ADC and FA changes in the genu may be due to loss of axonal integrity and vasogenic-like edema in the axons responsible for some intellectual functions. DTI may help clarify the underlying pathophysiology of CC changes in relation to neurocognitive function disorders in children with NF1.

Rare vascular pathology sinus pericranii; becomes symptomatic with pseudotumor cerebri.

Sinus pericranii (SP) is an uncommon vascular pathology that is characterized by a nodular structure emerging from the scalp. It is generally asymptomatic. Typically, it is aclose to soft, compressive, fluctuant swelling, intracranial sinus. The swelling increases during the Valsalva maneuver, jugular vein compression, coughing, or crying attacks. The diagnosis was confirmed by CT, MRI, and MR angiography. Here, we conclude that SP is a rare cause of headache and that the asymptomatic lesion become symptomatic as a result of association with pseudotumor cerebri.

Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.

Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six individuals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations.

MRS features during encephalopathic crisis period in 11 years old case with GA-1.

Glutaric aciduria type-1 (GA-1) is a disorder of amino acid metabolism. The usual clinical-onset is an acute encephalopathic crisis in early childhood. There are only a few cases diagnosed in older age groups. MRI features of the disease are well defined. However, there are limited number of studies concerning advanced neuroimaging findings. We present DWI and MRS findings of an 11 year-old GA-1 patient admitted with an encephalopathic crisis. Diffusion restrictions in bilateral basal ganglia, corpus callosum and periventricular deep white matter were observed. In left occipital periventricular white matter and left basal ganglia, mild increased Cho/Cr and MI/Cr ratios and decreased NAA/Cr ratio were detected. Also inverted double lactate peak (TE: 135 ms) was present at 1.33 ppm in the left basal ganglia. In addition to these findings, a peak at 1.56 ppm above the baseline was seen on both short and long echo-time MRS in left occipital lobe deep white matter which may show accumulation of degradation products of amino acids in the GCDH enzyme deficiency.

Prognosis and demographic characteristics of SSPE patients in Istanbul, Turkey.

AIM: SSPE is a rare progressive, invariably fatal long-term complication of measles infection. In this study, we assessed the demographic and prognostic characteristics of 64 consecutive SSPE patients diagnosed at a tertiary center. METHODS: The study had a retrospective design; data were obtained from patient records. RESULTS: The study includes 64 patients diagnosed with SSPE. There was history of consanguineous marriage in 27 (42.2%) patients. The average patient lifespan was 3.8years (45days-12years). The average patient age at diagnosis was 12.3 (range, 5-17)years. A statistically significant correlation was found between the age at diagnosis and lifespan (p=0.002). A statistically significant correlation was found between the incubation period and patient lifespan (p<0.001). No significant correlation was found between duration in the intensive care unit and lifespan (p=0.122). Routine physical therapy had no significant impact on the average lifespan (p=0.619). No significant difference was found between the vaccination dose and lifespan (p=0.651). CONCLUSIONS: High frequency of parental consanguinity in SSPE patients need to be evaluated as there might a genetic influence. Physical therapy and supportive treatments seems to have no affect on lifespan in SSPE patients. The age at diagnosis and incubation period might have an affect on prognosis and lifespan.

MRI findings in encephalopathy with primary carnitine deficiency: a case report.

BACKGROUND AND PURPOSE: We presented MRI and DWI findings of a 12-year-old boy with primary carnitine deficiency, manifested with hypoglycemic hypoketotic encephalopathy. METHODS: Magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) were performed to the patient. RESULTS: In our case, T2 hyperintensity and diffusion restriction were noted bilaterally in the corona radiate, cerebral white matter, deep white matter of cerebellum, ascending (inferior cerebellar peduncle) and descending tracts (corticospinal and corticobulbar tracts) of brainstem. CONCLUSIONS: MRI and DWI are helpful in the diagnosis, therapy planning and follow up of encephalopathic cases with carnitine deficiency.

The evaluation of physiological and biochemical parameters and the autonomic nervous systems of children with breath-holding spells.

AIM: The aim of this study was to investigate the physiological and biochemical parameters of children who are experiencing breath-holding spells (BHS) and to compare the function of their autonomic nervous systems with those of healthy children. PATIENTS AND METHODS: A total of 30 children (age range, 6 months-5 years) admitted for BHS were included in the study. The control group consisted of 30 age-matched and gender-matched healthy children. Each participant underwent a detailed physical examination as well as a laboratory evaluation. Echocardiography, electrocardiography (ECG), and electroencephalography were performed in the study group. The pilocarpine eye test was administered to each participant to detect autonomic dysfunction. RESULTS: No statistically significant differences were found between the groups for mean age, gender, and anthropometric measurements, nor for the biochemical parameters, including hemoglobin concentration, hematocrit, serum iron, transferrin saturation, ferritin, vitamin D, and vitamin B12 levels (p = 0.05). Compared with the control group, the study group showed significantly abnormal hypersensitivity of pupils after instillation of pilocarpine into their eyes (p = 0.01). CONCLUSION: Autonomic dysfunction existed in the children with BHS, but no correlation was found between BHS and deficiencies of iron, vitamin D, or vitamin B12.