Case report: Thrombotic microangiopathy in pediatric multisystem inflammatory syndrome associated with COVID-19: a case series.

Introduction: This report provides insight into three distinct pediatric cases exhibiting a nexus between multisystem inflammatory syndrome in children (MIS-C) and thrombotic microangiopathy (TMA) triggered by COVID-19. The aim is to underscore the range of clinical presentations and the essentiality of early interventions. Case presentations: This report presents three cases aged 10 months, 7 years, and 3 years with persistent fever, diarrhea, nausea, and vomiting. The first case, a 10-month-old girl, demonstrated acute kidney injury (AKI) and microangiopathic hemolytic anemia (MAHA) following a COVID-19 infection. Despite initial negative SARS-CoV-2 RT-PCR results, her condition escalated rapidly, presenting increased levels of LDH (peaking at 4,200 U/L) and requiring renal replacement therapy (RRT) to manage deteriorating renal function. Interventions with eculizumab and anakinra led to marked improvements, with a stable follow-up of 13 months post-hospitalization. The second case involved a 7-year-old girl who developed symptoms of MIS-C, hemolytic uremic syndrome (HUS), and posterior reversible encephalopathy syndrome (PRES) post-exposure to COVID-19, evidenced by heightened LDH levels (3,522 U/L at peak). After a precarious period of deteriorating kidney function and exacerbated hypertension, she responded positively to treatments, inclusive of IVIG, steroid therapies, and eculizumab, with a favorable 6-month follow-up showcasing stable laboratory results. The third case discusses a 3-year-old boy, without any medical history, manifesting HUS symptoms and COVID-19 infection. He exhibited increased LDH levels (peaking at 3,946 U/L) alongside elevated creatinine, marking renal impairment. He responded well to hemodialysis, IVIG, and steroid therapy, showcasing substantial recovery by the 19th day of hospitalization, which marked his discharge with a tapering steroid regimen. Conclusion: This case series underscores that MIS-C-associated TMA is a significant complication in pediatric COVID-19. Our findings illuminate the potential for treatment success but simultaneously emphasize the need for a more comprehensive understanding of the underlying pathophysiology.

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

Serum Zonulin Levels in Pediatric Migraine.

BACKGROUND: Migraine is a complex neurogenic inflammatory disorder. There are strong neuronal, endocrine, and immunologic connections between the brain and gastrointestinal system. Damage to the intestinal barrier is thought to cause systemic immune dysregulation. Zonulin is a protein produced by the small intestine epithelium in humans that regulates intestinal permeability through intracellular tight junctions and is a potential marker for inflammation. Zonulin increases in positive correlation with permeability. In our study, we aimed to research the correlation between serum zonulin levels in the period between attacks in pediatric patients with migraine. METHODS: The study included 30 patients with migraine and 24 healthy controls, matched in terms of sex and age. Demographic and clinical characteristics were recorded. Serum zonulin levels were studied with the enzyme-linked immunosorbent assay method. RESULTS: Patients had a mean of 5.6 ± 3.5 attacks per month. The mean serum zonulin was 5.68 ± 1.21 ng/mL in the migraine group and 5.72 ± 2.1 ng/mL in the control group with no significant difference found (P = 0.084). In the migraine group, no correlations were identified between serum zonulin levels and age, body mass index, pain frequency, pain duration, onset time, visual analog scale score, and presence of gastrointestinal systems apart from nausea-vomiting. CONCLUSIONS: More than 50 proteins were identified to affect the intestinal permeability apart from zonulin. There is a need for prospective studies encompassing the time of attack, but our study is important as it is the first study about zonulin levels in pediatric migraine.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

A Case with NAD(P)HX Dehydratase (NAXD) Deficiency: A Newly Defined Mutation in a Novel Neurodegenerative Disorder.

Introduction: Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are required redox equivalents for essential biochemical reactions. Their hydrated forms, NADHX and NAD(P)HX, are inhibitors for several dehydrogenases and cause harmful byproducts. NAD(P)HX dehydratase (NAXD) and NAD(P)HX epimerase (NAXE) together form the nicotinamide repair system. Case Presentation: A 7-month-old boy was admitted due to myoclonic seizures, impaired consciousness, and rapid loss of head control. One of his siblings regressed after a febrile seizure and died at 7 months. He had lethargy and axial hypotonia but skin lesions and organomegaly were not noted. Basal metabolic tests were within normal limits except serum and cerebrospinal fluid lactate levels, which were mildly elevated. Mitochondrial cocktail was added to the antiepileptic treatment with suspicion of mitochondrial disease. Whole-exome sequencing showed a novel homozygous mutation (c.247G>A) in the NAXD gene. His seizures stopped within a few weeks. However, he died at the age of 18 months. Discussion: Prominent features of NAXD deficiency are progressive neurological deterioration after fever, cardiomyopathy, skin lesions, and premature death. Unlike the cases reported in the literature, our patient had neither preceding fever nor skin lesion during follow-up. It appears that cases show phenotypic diversity.

How did the COVID-19 Pandemic Affect Pediatric Neurologists?

BACKGROUND: In addition to physical health, pandemics affect mental health. The aim was to reveal problems encountered during the coronavirus disease 2019 (COVID-19) pandemic by pediatric neurologists and pediatric neurology residents in Turkey. METHODS: Participants were sent a survey form using Google Forms between November 05, 2020, and December 07, 2020. The form included questions about demographic information, changes to services offered, effects of the COVID-19 pandemic on patient follow-up/treatment and doctor decision-making, the Depression-Anxiety-Stress Scale 21, and the Impact of Events scale for posttraumatic stress disorder. RESULTS: A total of 232 pediatric neurologists and residents (mean age: 40.67 ± 7.8 years) participated. Of these 182 participants (78.4%) stated the pandemic had affected decisions during diagnosis and treatment management. A total of 222 participants completed the Depression-Anxiety-Stress Scale 21 and Impact of Events scale. Of these, points at levels that were "severe and very severe" were present for 42 participants (18.9%) for depression, 29 participants for anxiety (13%), and 31 participants for stress (14%). Impact of Events scale points were high at "severe" levels for 122 participants (55%). All scores were higher for those with individuals at risk in terms of COVID-19 in their family compared with those without individuals at risk in the family (P < 0.05). CONCLUSIONS: As we emerge from the destruction caused by COVID-19, it will be beneficial not only for our professional practice but also in terms of our individual health to learn lessons that will assist in managing the next pandemic waiting in our future.

A Rare Pediatric Case of Severe Rhabdomyolysis Owing to Dual Infection.

AIM: We aimed to report a severe and rare pediatric rhabdomyolysis case associated with a dual viral infection. CASE: A 13 year-old, healthy girl presented with the complaints of fever, abdominal pain, weakness and dark-colored urine. She was diagnosed with rhabdomyolysis based on clinical signs and laboratory findings. The diagnosis was confirmed by serological tests and real-time polymerase chain reaction for Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Other potential genetic, metabolic and infectious causes were evaluated meticulously but no evidence was found. This case is also important as it is the first reported case to our knowledge on rhabdomyolysis associated with EBV and CMV co-infection in children. CONCLUSION: The presented case experienced tetraplegia due to the severe muscular damage and muscle power returned to normal range after 3 months. This suggests that EBV and CMV may have exert synergistic effects leading to more severe inflammation and degeneration.

Associations Between Transcranial Doppler Flow Velocities, Laboratory Parameters, and Clinical Features in Turkish Children With Sickle Cell Disease.

OBJECTIVE: Stroke is one of the major complications of sickle cell disease (SCD). Stroke features either occlusion of, or stenosis at, the origin of one of the large intracerebral arteries, the internal carotid artery (ICA), and/or the middle cerebral artery (MCA). PURPOSE: We sought correlations between cerebral blood flow velocities and the laboratory and clinical findings of patients with SCD. MATERIALS AND METHODS: Fifty-three pediatric SCD patients (39 with HbSS, 14 with HbSß0) were analyzed. The mean patient age was 12.9±3.9 years. The control group contained 24 healthy individuals. The time-averaged maximum mean velocity (TAMMV) and resistive index (RI) of the MCA, the TAMMVs of the ICA and vertebral artery (VA), and the diameter of the VA were estimated through transcranial Doppler ultrasonography using a 2.5 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. We evaluated the relationships between the TAMMVs, laboratory parameters, and clinical findings. RESULTS: The mean±SD MCA TAMMV was 161.2±35.4 cm/s in patients with HbSS and 185.8±62.9 cm/s in patients with HbSß0. The mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 168.5±43.9 cm/s, 0.63±0.06, 116.8±25.5 cm/s, 69.2±18.5 cm/s, and 3.5±0.61 mm for all SCD patients, respectively. In the control group, the mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 103.8±28.8 cm/s, 0.53±0.04, 96.4±27.8 cm/s, 40.3±12.1 cm/s, and 3.4±0.6 mm, respectively. Although the differences were not significant, TAMMVs were higher in HbSß0 patients taking hydroxyurea; those with hemoglobin levels <8 g/dL, ferritin levels >1000 ng/dL, mean platelet volume >12 fL, or red cell distribution width >18%; or required chelation, or were below the third percentiles of weight and height. The TAMMV was significantly higher only in SCD patients who complained of headache. CONCLUSIONS: High ferritin and low hemoglobin levels, a high mean platelet volume, a high red cell distribution width, low weight (below the third percentile), and a short height (below the third percentile) may be associated with elevated cerebral blood flow velocities and an increased stroke risk in children with SCD. Children with such features should be closely followed-up through transcranial Doppler ultrasonography examination.

Assessment of PELOD-2 and PIM-3 scores of children coming from the war in Syria.

OBJECTIVES: Since the civil war in Syria began, millions of Syrians have left the country and been forced to migrate to other countries. Turkey is the country with the most refugees hosting 3.6 million refugees. This study aimed to compare the PIM-3 score, PELOD-2 score, PELOD-2 predicted death rate (PDR), mortality rates, demographic data, and outcomes of patients admitted to pediatric intensive care units between refugee children living in Turkey, pediatric patients brought directly from the border by the emergency services, and the general Turkish population. METHODS: This was a retrospective study performed between February 2018 and February 2019 at Hatay State Hospital, very close to the Syrian border. The study included 158 patients. Patients were divided into three groups: Turkish citizens, those living in Turkey as refugees, and those brought from the border. RESULTS: Of the patients, 57 were Turkish citizens, 33 were refugees, and 68 were brought from the border. For patients, the mean PIM-3 score was 25.62±27.70, the PELOD-2 score was 8.03±4.72, and PELOD2-PDR was 16.07±23.45. The median scores for PIM-3, PELOD-2, and PELOD2-PDR of patients brought from the Syrian border were higher compared with Turkish citizens and refugees. There was no significant difference between refugees and Turkish citizens. Of the patients, 27 died, with the distribution being 15% Turkish citizens, 26% refugees, and 59% brought from the border. The mortality of patients transported from the border was statistically significant (P=0.03). CONCLUSION: We consider that the source of the difference between patients brought from the border and those living in Turkey may be associated with the continuing war beyond our borders and children experiencing insufficient care conditions. In conclusion, it is not just weapons that cause death in war, and children unfortunately suffer because of this situation.

Sublingual Atropine Sulfate Use for Sialorrhea in Pediatric Patients.

Sialorrhea is a frequent problem and may lead to aspiration in patients with swallowing dysfunction. We aimed to assess the effectiveness and safety of sublingual atropine sulfate treatment in pediatric patients with sialorrhea. The medical records of patients who had received sublingual atropine sulfate between January 2015 and January 2016 were reviewed retrospectively. The demographic properties, diagnosis, invasive or noninvasive mechanical ventilation need, and the presence of tracheotomy were assessed. Response rates to sublingual atropine were measured using the Teacher Drooling Scale (TDS). Pre and post-treatment drooling scores were compared. Atropine sulfate ampoule was administered at 20 µg/kg/dose. Minimum dose was 0.25 mg, while maximum dose was 0.03 mg/kg.Thirty-five pediatric patients with sialorrhea who had received sublingual atropine sulfate were identified; however, TDS scores had been recorded in only 20 of them. The median age of the patients was 25 months (3-78 months; 7 girls, 13 boys). Sixteen (80%) patients were on invasive mechanical ventilation and seven (30%) had tracheotomy. Nineteen patients had a neurodevelopmental disorder and only one patient had oral and esophageal lesions due to corrosive material intake. The median TDS score prior to sublingual atropine sulfate treatment was 5, and it decreased to 3 on the second day of treatment, a change that was statistically significant ( p < 0.001). No side effects were observed. Sublingual atropine sulfate is safe and effective in the short-term treatment of sialorrhea; however, randomized placebo controlled and long-term follow-up studies are necessary.

Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies.

BACKGROUND AND AIMS: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam. METHOD: LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. RESULTS: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group. CONCLUSION: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Hashimoto's encephalopathy presenting as pseudobulbar palsy.

INTRODUCTION: Hashimoto's encephalopathy (HE) is an autoimmune condition with varied neurological and psychiatric features. HE is very unusual as a cause of pseudobulbar palsy (PSP). CASE PRESENTATION: A 14-year-old male was admitted with right-sided weakness, dysphagia, speech disorder, and aggressiveness. Brain magnetic resonance imaging showed increased intensity in bilateral temporal, insular cortex, amygdala, and parahippocampal area on T2-weighted and fluid-attenuated inversion recovery images. Autoimmune encephalitis was considered as the patient had subacute onset of psychiatric and motor disturbances with normal findings for cerebrospinal fluid. N-methyl-D-aspartate receptor, anti-glutamate-type α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2, anti-contactin-associated protein-like 2, anti-gamma-aminobutyric acid receptor, anti-Leucine-rich, and glioma-inactivated 1 antibodies were negative but the anti-thyroperoxidase (antiTPO) level was greater than 998 IU/ML (n:0-9). Steroid therapy was initiated as pulse therapy and maintained with 2-mg/kg/day dose with the diagnosis of HE. He was symptom free for 6 months. In the follow-up period, he had two recurrences which responded to steroid therapy. CONCLUSION: The common causes of PSP are demyelinating, vascular, and motor neuron diseases and congenital malformations of the opercular or insular cortex. However, there are no cases of PSP developing after any autoimmune encephalitis. This case highlights the importance of early detection of antiTPO antibodies with the findings of PSP due to autoimmune encephalitis.

The role of inflammatory biomarkers in CHD-associated pulmonary hypertension in children.

OBJECTIVE: The present study aims to identify the role of inflammatory markers such as C-reactive protein, interleukin-6, and fractalkine in CHD-associated pulmonary hypertension in children. METHODS: This is a prospective review of 37 children with CHD-related pulmonary hypertension, 21 children with congenital heart defects, and 22 healthy children. RESULTS: Serum C-reactive protein and interleukin-6 levels were significantly higher in the children with CHD-related pulmonary hypertension (respectively, p=0.049 and 0.026). Serum C-reactive protein concentrations correlated negatively with ejection fraction (r=-0.609, p=0.001) and fractional shortening (r=-0.452, p=0.007) in the pulmonary hypertension group. Serum fractalkine concentrations correlated negatively with ejection fraction (r=-0.522, p=0.002) and fractional shortening (r=-0.395, p=0.021) in the children with pulmonary hypertension. Serum interleukin-6 concentrations also correlated negatively with Qs (r=-0.572, p=0.021), positively with Rs (r=0.774, p=0.001), and positively with pulmonary wedge pressure (r=0.796, p=0.006) in the pulmonary hypertension group. A cut-off value of 2.2 IU/L for C-reactive protein was able to predict pulmonary hypertension with 77.5% sensitivity and 77.5% specificity. When the cut-off point for interleukin-6 concentration was 57.5 pg/ml, pulmonary hypertension could be predicted with 80% sensitivity and 75% specificity. CONCLUSION: Inflammation is associated with the pathophysiology of pulmonary hypertension. The inflammatory markers C-reactive protein and interleukin-6 may have a role in the clinical evaluation of paediatric pulmonary hypertension related to CHDs.

Complete paralytic botulism mimicking a deep coma in a child.

Botulism is a rare cause of neuroparalysis. Delay in diagnosis and treatment exerts adverse impact on mortality and morbidity. We report a child with complete flaccid paralysis followed by progression to coma-like consciousness. The patient required mechanical ventilation. As serological tests could not be performed, detailed history and physical examinations led to the suspicion of botulism, and repetitive nerve stimulation tests supported the diagnosis. Botulinum antitoxin was administered. The patient`s neuromuscular function improved rapidly.