Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases.

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study.

Children with chronic neurological diseases, including cerebral palsy (CP), are especially susceptible to vaccine-preventable infections and face an increased risk of severe respiratory infections and decompensation of their disease. This study aims to examine age-appropriate immunization status and related factors in the CP population of our country. This cross-sectional prospective multicentered survey study included 18 pediatric neurology clinics around Turkey, wherein outpatient children with CP were included in the study. Data on patient and CP characteristics, concomitant disorders, vaccination status included in the National Immunization Program (NIP), administration, and influenza vaccine recommendation were collected at a single visit. A total of 1194 patients were enrolled. Regarding immunization records, the most frequently administrated and schedule completed vaccines were BCG (90.8%), hepatitis B (88.9%), and oral poliovirus vaccine (88.5%). MMR was administered to 77.3%, and DTaP-IPV-HiB was administered to 60.5% of patients. For the pneumococcal vaccines, 54.1% of children received PCV in the scope of the NIP, and 15.2% of children were not fully vaccinated for their age. The influenza vaccine was administered only to 3.4% of the patients at any time and was never recommended to 1122 parents (93.9%). In the patients with severe (grades 4 and 5) motor dysfunction, the frequency of incomplete/none vaccination of hepatitis B, BCG, DTaP-IPV-HiB, OPV, and MMR was statistically more common than mild to moderate (grades 1-3) motor dysfunction (p = 0.003, p < 0.001, p < 0.001, p < 0.00, and p < 0.001, respectively). Physicians' influenza vaccine recommendation was higher in the severe motor dysfunction group, and the difference was statistically significant (p = 0.029).Conclusion: Children with CP had lower immunization rates and incomplete immunization programs. Clinicians must ensure children with CP receive the same preventative health measures as healthy children, including vaccines. What is Known: • Health authorities have defined chronic neurological diseases as high-risk conditions for influenza and pneumococcal infections, and they recommend vaccines against these infections. • Children with CP have a high risk of incomplete and delayed immunization, a significant concern given to their increased healthcare needs and vulnerability to infectious diseases. What is New: • Influenza vaccination was recommended for patients hospitalized due to pneumonia at a higher rate, and patients were administered influenza vaccine more commonly. • Children with CP who had higher levels of motor dysfunction (levels 4 and 5) were more likely to be overdue immunizations.

Topiramate-Responsive Tremor in a Novel Pathogenic Variant of SPG15 Patient.

Hereditary spastic paraplegia (HSP) is group of a rare neurodegenerative disorder with both genetically and clinically diverse neurologic features. Indeed, disease progression is varying greatly within the different forms and current treatment modalities are exclusively symptomatic for HSP. Tremor in HSP patients is only mentioned with rare case reports, so treatment option is lack in clinical ground. We reported a case of a HSP-15 girl with a previously reported novel mutation of SPG15 complained of a life disturbing tremor and topiramate as a drug therapy for tremor in our HSP patient.

Pediatric case of persistent hiccups associated with hypertrophic olivary degeneration.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare degenerative disorder that is thought to occur subsequent to a disruption of the dentate-rubro-olivary pathway. CASE: We report a pediatric case of unilateral HOD presented with persistent hiccups and palatal tremor. Radiological examination of diaphragm was normal considering ultrasound and chest x-ray. On T2WI (weighted images) and Fluid Attenuated Inversion Recovery (FLAIR) images, hyperintense enlargement of the right inferior olivary nucleus was seen. No abnormal enhancement was detected on post-contrast scans and no evidence of restricted diffusion was seen. Susceptibility weighted imaging (SWI) sequences revealed a chronic hemorrhage involving the medulla oblongata and cerebellum. Cranial magnetic resonance imaging (MRI) findings were consistent with unilateral HOD. Palatal tremor and dentate-rubral tremor are frequent presentation of HOD, however to our knowledge persistent hiccups had not yet been reported in children with HOD. CONCLUSION: We highlight a pediatric case of unilateral HOD, which presented with persistent hiccups. Awareness of clinical and radiological findings of HOD is important to avoid misinterpretation as a mass lesion, an ischemic event, or a demyelinating disease and provide adequate management.

The Clinical and Molecular Characteristics of Molybdenum Cofactor Deficiency Due to MOCS2 Mutations.

BACKGROUND: We explored the clinical and molecular characteristics of molybdenum cofactor deficiency due to MOCS2 muations. METHODS: We summarize the genetic and clinical findings of previously reported patients with a MOCS2 mutation. We also present a new patient with novel neuroradiological findings associated with molybdenum cofactor deficiency due to a novel homozygous variant in the 5' untranslated region of the MOCS2 gene. RESULTS: The study population comprised 35 patients with a MOCS2 gene mutation. All reported children had delayed motor milestones. The major initial symptom was seizures in neonatal period. Facial dysmorphism was present in 61% of the patients. Only one patient had ectopia lentis. Agenesis of the corpus callosum and an associated interhemispheric cyst in our case are novel neuroradiological findings. CONCLUSIONS: The occurrence of neonatal seizures and feeding difficulties can be the first clinical signs of molybdenum cofactor deficiency. Although there is no effective therapy for this condition, early diagnosis and genetic analysis of these lethal disorders facilitate adequate genetic counseling.

Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study.

Objective To investigate the relationship between brain masculinization and retinal thickness in children with congenital adrenal hyperplasia (CAH). Methods Forty-five patients with CAH aged between 4 and 18 years and 30 age-matched healthy controls were included in this prospective study. Macular area was examined with optical coherence tomography (OCT); central subfield thickness (CST), cube volume (CV) and macular retinal thickness (MT) were measured in each subject. A gender identity questionnaire (GIQ) was used for the evaluation of gender happiness index. Results Girls with CAH had a higher CV (p = 0.002) and MT (p = 0.003) than healthy girls. No significant difference was found between boys with CAH and healthy boys regarding the retinal thickness measurements. Mean CST, CV and MT were significantly higher in boys than in girls in the control group (p = 0.013, p < 0.001, respectively), but there was no significant difference in those parameters between girls and boys with CAH. The gender happiness index was not different between healthy boys and boys with CAH, but was significantly lower in girls with CAH than healthy girls (p = 0.01). Conclusions As retina is part of the brain, our finding appears to be a morphological evidence of the excess androgen exposure on brain structures in girls with CAH. In addition, we suggest using retinal thickness measurements as a marker of prenatal excess androgen exposure in future studies.

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.

Possible effects of neonatal vitamin B12 status on TSH-screening program: a cross-sectional study from Turkey.

BACKGROUND: In this study we evaluated whether vitamin B12 deficiency affects neonatal screening (NS) for congenital hypothyroidism (CH). METHODS: A cross-sectional study conducted from 2010 to 2011. A total of 10,740 infants were born in our hospital in this period. Thyroid-stimulating hormone (TSH) was tested for NS and neonates with abnormal screening results (TSH>20 mIU/L) were re-examined. Two hundred and twenty-nine re-called subjects (re-call rate 2.3%) were compared to 77 randomly selected newborns with normal TSH screening among these term newborns in terms of serum TSH, free T4, vitamin B12 and homocysteine status. RESULTS: Of the 229 re-called subjects, 11 infants with CH and 21 infants with transient TSH elevation were detected. In the normal TSH screening group, only two infants were diagnosed with transient TSH elevation. Mean serum B12 levels were 126.4±48.7 pg/mL and 211.9±127.9 pg/mL in the positive TSH-screening group and the control group, respectively. There was a significant difference between positive and normal TSH-screening groups in regard to serum TSH, free T4, serum B12 and homocysteine levels. CONCLUSIONS: We found a significant vitamin B12 deficiency in positive TSH-screening infants. Beside the crucial role of vitamin B12 in newborns, deficiency seems to increase the recall rates of infants in an NS program for CH.

Seroprotection status of hepatitis B and measles vaccines in children with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is speculated to have an impaired immunological response to vaccines. This paper aimed to investigate the presence of specific antibodies against hepatitis B virus (HBV) and measles in diabetic children who had been immunized according to the standard national calendar of immunization. METHODS: Two hundred and one diabetic children and 140 healthy controls were prospectively evaluated. Antibodies against hepatitis B (anti-HBs) and measles were detected in all individuals who completed the vaccination schedule. We noted onset of T1DM, duration of the disease, diabetes-related autoantibodies and mean HbA1c levels. RESULTS: Some 72.6% of diabetics and 82.1% of controls had anti-HBs (+) (p=0.04). We found a reduced efficacy of measles vaccination in anti-HBs (-) diabetic children (p=0.009), even though there was no significant difference between the study and control groups. Onset of the disease was earlier in anti-HBs (-) diabetics than in controls (p=0.038). No difference with respect to other parameters was found. CONCLUSIONS: Our data showed a reduced seroprotection rate for HBV vaccination in diabetic children and for measles with anti-HBs (-) diabetics. Larger studies should be encouraged to confirm the vaccine efficacy in diabetic children and to elucidate possible pathogenic mechanisms.

Recognizing the psychosocial aspects of type 1 diabetes in adolescents.

OBJECTIVE: Considering the ever increasing population of diabetic adolescents and the association of the disease with psychosocial problems throughout its course, depression and/or anxiety and social support from parents are issues of special concern in these patients. The study aimed to identify the depression and anxiety state of diabetic adolescents and its impact on the management of diabetes mellitus (DM). METHODS: 295 adolescents with type 1 DM and their parents attended our study. Psychological distress was assessed using the Children's Depression Inventory and the State-Trait Anxiety Inventory (STAI I-II) for Children, Perceived Social Support from Family (PSS-Fa) scale, Beck Depression Inventory for adults, STAI I-II for adults and the Multidimensional Scale of Perceived Social Support (MSPSS). Records of glycemic measurements, insulin dosage and hemoglobin A1c levels were used as glycemic control parameters. RESULTS: Depression rate was 12.9%. State (p<0.001) and trait anxiety (p<0.001) levels were high; PSS-Fa (p<0.001) and MSPSS (p<0.006) scores were low in the depressive patients. Positive correlations were noted between depression, PSS-Fa, STAI-I and STAI-II. CONCLUSION: Therapeutic strategies of DM should include co-existing psychiatric conditions throughout the course of the disease. In diabetic adolescents, PSS-Fa, STAI-I and STAI-II appear to be effective tools in the evaluation of depression.

Comparison between daily supplementation doses of 200 versus 400 IU of vitamin D in infants.

The daily supplementation of vitamin D is mandatory for infants. However, there are still conflicting opinions about the exact daily dose. Thus, we aimed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day. One hundred and sixty-nine infants were randomly assigned to two groups (group 1, 200 IU/day; group 2, 400 IU/day) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139. The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months (group 1, 39.60 mcg/L; group 2, 56.55 mcg/L; p < 0.0001). We clearly demonstrated that at the age of 4 months, none of the infants on the group 2 had a serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However, 21.3% of the infants in group 1 had a level below 30 mcg/L. Thus, in order to avoid vitamin D deficiency and rickets, we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose.

Effects of selenium supplementation in the early stage of autoimmune thyroiditis in childhood: an open-label pilot study.

AIM: The aim of the study was to evaluate the role of selenium (Se) in childhood autoimmune thyroiditis regarding its effect on thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb), and thyroid morphology. METHODS: Newly diagnosed 23 euthyroid children (mean age, 12.3 +/- 2.4 years) with Hashimoto thyroiditis (HT) received only 50 microg L-selenomethionine per day for 3 months. The baseline basal urinary iodine level, serum Se, TSH, fT4, TPOAb, and TgAb concentrations, and thyroid morphology by ultrasound were detected. We reanalyzed the TPOAb and TgAb changes at the 3rd month and then compared the thyroid morphology with 30 healthy individuals (mean age, 12.1 +/- 2.1 years) at the 6th month. RESULTS: Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of > or = 30%. CONCLUSION: In terms of TPOAb and TgAb, Se may not benefit in the euthyroid period of HT, but Se supplementation seems to lead a favorable response in thyroid volume regression.

Ovarian and uterine ultrasonography and relation to puberty in healthy girls between 6 and 16 years in the Turkish population: a cross-sectional study.

AIM: To investigate uterine and ovarian ultrasonography in healthy girls and establish reliable cut-off limits in the Turkish population. METHODS: The study was performed on 90 girls between 6 and 16 years of age with bone age, hormonal evaluation and pelvic ultrasounds. Total uterine length (TUL), anteroposterior diameters of corpus (COAP), anteroposterior diameters of cervix (CEAP), fundus/cervix ratio (F/C), uterine volume (UV), ovarian volume (OV) and morphology were obtained. The data were stratified according to various pubertal stages and ages. RESULTS: Age-related increases of pelvic organs were noted after 10-10.9 years. Significant correlation was detectable between age and OV, TUL and UV in pubertal girls, but age only correlated with OV in prepubertal girls. A cut-off value of 4 cm for TUL, 2.57 cm(3) for UV and 1.58 cm(3) for OV were the best discrimination values for entering puberty. CONCLUSION: The data herein may be useful in screening cases around puberty when continuous changes take place.

Subclinical hypothyroidism in in vitro fertilization babies.

AIM: Assisted reproduction technology is used widely all over the world. There is a great concern about the morbidity of in vitro fertilization (IVF) babies, but investigations are mostly related to mechanical conditions that are attributed to multiparity. This paper aimed to investigate the effect of IVF on thyroid functions in newborns. METHODS: A total of 98 healthy, term IVF newborns were evaluated between postnatal 2-4 weeks of age by screening of thyroid functions between July 2006 and April 2008. Ten subjects were assessed as a study group whose thyroid-stimulating hormone (TSH) levels were higher than 6.5 mU/L. Control group consisted of randomly selected 10 naturally conceived infants with hyperthyrotropinemia (whose TSH levels were higher than 6.5 mU/L but under 15 mU/L) with the same age. All children were thoroughly examined, and serum fT4, TSH, anti-thyroid peroxidase and anti-thyroglobulin antibodies were measured, and a thyrotropin-releasing hormone (TRH) test was performed in all subjects in both groups. RESULTS: Euthyroid hyperthyrotropinemia was diagnosed in approximately 10% of IVF babies. Exaggerated TSH levels to TRH were obtained in all IVF babies (subclinical hypothyroidism) but in none of the controls. A significant difference was noted in the concentration of TSH at the 20th min between the two groups (p < 0.001). Besides, sustained and delayed TSH responses were observed in IVF babies. Neonatal screening tests were negative in both of the groups. CONCLUSION: In IVF babies, despite normal neonatal screening tests, subclinical hypothyroidism might be observed that suggests the need for screening in this respect.

Miliaria rubra and thrombocytosis in pseudohypoaldosteronism: case report.

Pseudohypoaldosteronism type 1 (PHA1) is a disease involving a state of renal tubular unresponsiveness to the action of aldosterone and characterized by excessive salt loss in the urine, hyperkalemia, and metabolic acidosis. In kidney, PHA1 may occur primarily by mutations in the subunits of the sodium channel or in the mineralocorticoid receptors, and secondarily by several renal disorders. Miliaria rubra and thrombocytosis are reported in a 6-month-old girl with PHA1. In patients with PHA1, miliaria rubra-like cutaneous eruptions are suggested to occur due to obstruction of eccrine sweat glands through inflammation caused by excessive sodium excretion in sweat during hyponatremic crises. The presence of thrombocytosis in patients with PHA1 has not been previously reported. A hypothesis is proposed suggesting that sympathetic activation which provides vascular tonus during sodium excretion in sweat and salt-depletion crisis may play a role in the development of eruptions and thrombocytosis in patients with PHA1.

Arachnoid cysts in childhood with endocrinological outcomes.

Arachnoid cysts are mainly manifested with the consequent neurological disorders. Even though these cysts may interfere in many systems due to their localizations, there is little information concerning their involvement in endocrinological disorders. We emphasize endocrinological functions together with cyst localizations and neurological disorders in childhood. A total of 50 patients diagnosed with arachnoid cysts were screened for cyst localizations, neurological symptoms and endocrinological outcomes evaluated by pubertal and growth status and hypothalamopituitary insufficiency. We investigated the interactions of these parameters. Arachnoid cysts were localized mostly in the middle fossa (54%) and posterior fossa (26%). Middle fossa cysts had a strong predilection for male gender (66.7% male) and left hemispheric dominancy (77%). We detected growth hormone deficiency in six patients, obesity in six patients and central precocious puberty in one patient; cysts were in the temporal area in three of the obese cases. All patients in our study had normal levels of cortisol, thyroid hormones and prolactin. In pediatric patients with arachnoid cysts, endocrinological follow-up is crucial as neurological outcomes and further evaluations are needed, mainly to confirm pubertal and growth status.

Imaging findings after fascial injection of tetanus vaccine.

Adverse reactions to vaccines vary from mild to fatal. Local reactions are often due to hypersensitivity to the adjuvant substances in the vaccine. This case report aims at illustrating the imaging findings of a fascial injection of the tetanus vaccine. A 14 year-old boy, vaccinated 6 months previously presented with a mass lesion in the left deltoid area. Magnetic resonance imaging and ultrasonographic evaluations were performed and the findings were characteristic for fascial granuloma. The histopathologic examination confirmed the diagnosis. In our knowledge, this is the first case of granuloma post intrafascial injection of tetanus vaccine which was MRI and ultrasonographic evaluated and histopathologicly confirmed.

A case of late-onset central hypoventilation syndrome with hypothalamic dysfunction: through a new phenotype.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder with uncertain nosology that usually presents early in life. The syndrome is characterized by ventilatory response impairment to carbon dioxide and may result in respiratory failure at birth. Recent reports have identified a similar clinical presentation beyond infancy called late-onset central hypoventilation syndrome (LO-CHS) as a disease continuum of CCHS with similar and overlapping pathophysiology. However, some have proposed that the syndrome accompanied by hypothalamic dysfunction (HD) be classified as a distinct clinical entity, LO-CHS/HD. To the best of our knowledge, the case reported herein is the oldest case of LO-CHS/HD in childhood, at 13 years old. He suffered from recurrent pulmonary edema, acute convulsive seizures, hypersomnia, hyperphagia, obesity, impaired glucose tolerance test, and hypercapnia, diagnosed as LO-CHS/HD, and was successfully treated with nasal bi-level positive airway pressure.

Is daily 400 IU of vitamin D supplementation appropriate for every country: a cross-sectional study.

BACKGROUND: Vitamin D deficiency in childhood is a significant problem worldwide. Religious, social customs, and lack of food fortification were significant hurdles in the way of the rickets scourge. Recent data support a serum level of 25(OH)D level > 40 ng/mL as the appropriate standard to achieve to prevent rickets. Herein, the current approaches of preventing rickets and optimal level of different vitamin D intakes were evaluated. METHODS: A total of 148 fully breastfed, healthy children between age of 2-24 months were investigated by screening serum 25(OH)D from April 1 to May 31, 2006. Three groups were composed according to ages (2-6, 6-12, 12-24 months), and those groups were paired with three subgroups established according to vitamin D intake of ≤300, 400, and 600 IU/day. Vitamin D status was evaluated with regard to cut-off value of 15 ng/mL and 40 mg/dL. The clothing types and vitamin D supplementation of mothers were recorded. RESULTS: We found that 27.3% of cases in 2-6 months, 8.3% in 6-12 months and 30% in 12-24 months had 25(OH)D <15 ng/mL and 54.5, 33.3, and 50% of cases were <40 ng/dL with 400 IU/day vitamin D intake. With 600 IU/day supplementation, 14.3, 10.3, and 4.8% of cases had 25(OH)D <15 ng/mL, respectively. CONCLUSION: Vitamin D intake of 400 IU/day seems to be favorable at the first year in breastfed children but vitamin D deficiency was still evident after prophylaxis. Vitamin D supplementation should be at least 600 IU/day in Turkey, and nutrition policy should focus on the food fortification with vitamin D.