Optic Nerve Sheath Diameter and Retinal Artery Resistive Index Measurements with Bedside Ophthalmic Ultrasound in Pediatric Patients with Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome (PTCS) is characterized by raised intracranial pressure (ICP) with no neuroradiological abnormalities. Ocular ultrasound has been in use to measure optic nerve sheath diameter (ONSD), and retinal artery Doppler indices have been used for indirect assessment of ICP by pediatric intensivists. Here, we aimed to evaluate the correlation of the lumbar puncture (LP) opening pressure with the ultrasonographic ONSD and retinal resistive index (RRI) measures in patients with PTCS. And we wanted to find an answer to the following question: Can ultrasonographic ONSD measures serve as a follow-up tool in patients with PTCS? A prospective, single-center, case-control study was performed by pediatric intensive care and pediatric neurology departments. A total of 7 patients with PTCS were evaluated as patient group and 15 healthy children were evaluated as control group. The mean age of patient group was 138.8 ± 43.7 months. The mean right ONSD was 6.7 ± 0.5 mm and the mean left ONSD was 6.7 ± 0.6 mm. The mean right RRI value was 0.73 ± 0.03 and the mean left RRI was 0.73 ± 0.09. For the patient group, ONSD and RRI values of both eyes were statistically significant higher values than for the control group. The mean LP opening pressure was 56.57 ± 16.36 cmH 2 O. We detected strong, positive, and statistically significant correlations between the LP opening pressure and ONSD baseline measures for both the right eye ( r = 0.882, p = 0.009) and the left eye ( r = 0.649, p = 0.004). There was no correlation between opening pressure in LP and RRI measurements. We detected a statistically significant decrease in the right ONSD and left ONSD values and visual analog scale scores at the third-month follow-up. Our study results demonstrate that ultrasonographic ONSD measurements can be used as a noninvasive tool for assessment of the ICP at first admission and can be used as a follow-up tool in PTSC patients.

Dynamic thiol/disulphide homeostasis in children with neurofibromatosis type 1 and tuberous sclerosis.

Neurofibromatosis type 1 (NF1) and tuberous sclerosis (TSC) are autosomal dominant neurocutaneous diseases. Epilepsy, malignancy and other neurological complications are common in both diseases. We aimed to investigate the thiol/disulphide balance as an oxidative stress marker in children who suffer from NF1 and TSC. Twenty-two patients with NF1, 20 TCS, and 22 healthy control subjects were included in the study. The total thiol, native thiol, and disulphide levels were measured and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated and compared in three groups. The mean age and sex distribution of the patients with TSC and NF1 and the healthy control were similar. The total thiol, native thiol, and disulfide level was lower in TSC and NF1 group than the healthy control group. There were no significant differences among disulphide/native thiol and disulphide/total thiol ratios of three groups. We detected that the total thiol, native thiol, and disulfide levels were lower in TSC and NF1 group than the healthy control group. These results indicate that dynamic thiol-disulphide homeostasis can be used as a marker of oxidative stress in clinical trials with TSC and NF1.

Factors affecting epilepsy prognosis in patients with tuberous sclerosis.

PURPOSE: We aimed to determine the characteristics of epileptic seizures that significantly affect the cognitive functions of 83 patients followed with tuberous sclerosis complex (TSC), their resistance to treatment and risk factors causing this resistance. MATERIALS-METHODS: In order to determine the prognosis, the seizure-free/seizure-controlled group and the group with refractory seizures were compared. In addition, risk factors affecting cognitive functions in the patients were determined. RESULTS: There was a statistical significance between the presence of a history of seizures in the neonatal period, the age of onset of seizures being less than 2 years of age, autism, status epilepticus, Lennox-Gastaut syndrome (LGS), presence of infantile spasm, generalization of the electroencephalography (EEG) findings, the number of tubers in cerebral imaging being more than three and refractory seizures (p < 0.05). Statistically significant relationship was found between presence of a history of seizures in the neonatal period, the age of onset of seizures, autism, LGS, presence of infantile spasm, presence of status epilepticus history, history of using more than three antiepileptic drugs, generalization of EEG findings, presence of SEGA in cerebral imaging, number of tubers being more than three and the patient's mental retardation (p < 0.05). CONCLUSION: In logistic regression analysis, the age of the seizure onset being less than 2 years of age, the presence of autism and number of tubers being more than three in cerebral magnetic resonance imaging (MRI) are determined to be the risk factors that most likely to increase the seizures to be more resistant.

Neurofibromatosis type 1 and cardiac manifestations.

OBJECTIVE: Cardiac manifestations of neurofibromatosis type 1 (NF1) may include hypertension, congenital heart disease, and hypertrophic cardiomyopathy. The aim of this study was to evaluate cardiac abnormalities in patients with NF1. METHODS: Sixty-five NF1 patients (mean age: 9±4.48 years) were retrospectively studied. Standard electrocardiography and echocardiography were performed in all patients. RESULTS: Cardiac abnormalities were found in 11 of the 65 patients (15.3%). Five patients had mitral valve regurgitation, 2 patients had secundum atrial septal defect, 1 patient had pulmonary valvular stenosis, 1 patient had ventricular septal defect, 1 patient had tricuspid valve regurgitation, and 1 patient had aortic valve regurgitation. CONCLUSION: Cardiac abnormalities have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, for any patient with NF1, a cardiologic assessment is mandatory at the time of diagnosis and with regular follow-up intervals.

Giant axonal disease: Report of eight cases.

BACKGROUND: Giant axonal neuropathy (GAN) is an autosomal recessive inherited progressive motor and sensory neuropathy with typical onset in early childhood. The disease is caused by GAN gene mutations on chromosome 16q24.1. To determine clinical and genetic results in Turkish patients with GAN. METHODS: Eight children with GAN were retrospectively analyzed. Five (62.5%) were girls and 3 (37.5%) were boys with the mean age on admission 10.13±3.8 years (range: 5-15 years). RESULTS: Parental consanguinity was found in all the families. The patients had the classical clinical phenotype characterized by a severe axonal neuropathy with kinky hair. Two patients had contractures of extremities, and not walking. One patient was walking with aid. The other patients were walking without aid. Mutation analysis was performed in two patients and IVS9 (+1G>T) (homozygous) mutation was detected. CONCLUSION: The classical clinical findings allowed considering the GAN diagnosis, but, in atypical cases and milder phenotypes, the presence of giant axons in nerve biopsy was helpful to specify molecular analysis.

Multiple sulfatase deficiency: A case series of four children.

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.

Oncologic manifestations in children with neurofibromatosis type 1 in Turkey.

Children with neurofibromatosis type 1 (NF1) are predisposed to malignancies such as brain tumors, leukemia, and pheochromocytomas. The aim of this study was to evaluate malignancy in patients with NF1. We studied 120 patients with NF1 in this study. Demographic data from these patients were retrospectively reviewed. We found 20 malignancies in 19 patients in our study. Ten children with NF1 had optic glioma. Four children had solid central nervous system tumors (3 pilocytic astrocytomas, 1 glioblastoma multiforme). Three patients had myeloid malignancies (1 juvenile myelomonocytic leukemia, 1 acute myeloid leukemia, 1 acute lymphocytic leukemia). Hodgkin lymphoma, T-cell lymphoblastic lymphoma, and malignant triton tumor were found in one patient each. Patients with NF1 are predisposed to both benign and malignant tumors of neurogenic and non-neurogenic origin. Therefore, systematic medical follow-up in patients with NF1 is important.

Pseudoarthrosis of the hand in neurofibromatosis type 1: a case report.

Neurofibromatosis (NF) is a disorder with a wide spectrum of clinical manifestations. Here, we describe a 16-year-old boy with NF1 who had pseudoarthrosis of the 4th and 5th fingers of the left hand. He had specific cutaneous lesions and Lisch nodules in the iris. Because NF1 affects multiple organ systems, patients are likely to benefit most from a multidisciplinary treatment strategy.

Joubert syndrome: report of 11 cases.

Joubert syndrome (JS) is an autosomal recessive condition characterized by hypotonia, ataxia, psychomotor delay, and variable occurrence of oculomotor apraxia and neonatal breathing abnormalities. The 11 cases were searched according to their clinic, radiologic, and mutation analysis findings, according to which they were diagnosed as JS. Physical, neurological and fundus examinations were performed in all patients. Cerebral magnetic resonance imaging scan, abdominal ultrasonography, and if necessary, echocardiography were performed. CC2D2A and ARL13B mutations were analyzed in our 11 JS patients. The mean age was 31.09 ± 37.49 months (range: 1 month - 10 years). Two of the cases were siblings. Nine of the cases had a history of episodic hyperpnea. The other findings were hypotonia, ataxia, psychomotor retardation, and nystagmus. In all patients, the "molar tooth sign" was observed with scanning methods. In addition, cerebellar cortical dysplasia was established in one of the cases. Macrocephaly (1 patient), multiple renal cysts (1 patient), ocular coloboma (2 patients), ptosis (1 patient), congenital heart disease (1 patient), polydactyly (2 patients), and congenital hip dislocation (2 patients) were also determined. We identified mutation (c.C4452T → p.R1518W) in CC2D2A in two patients. JS can show heterogeneity clinically, neuroradiologically and genetically. Determination of the symptoms, early diagnosis and genetic consultation are the goals for decision-making to begin treatment and rehabilitation programs.

Evaluation of sixteen children with pseudotumor cerebri.

Pseudotumor cerebri (PTC) is a clinical condition characterized by signs and symptoms of increased intracranial pressure, such as headache and papilledema. A total of 16 patients diagnosed with PTC [12 (75%) female; 4 (25%) male] were included in the study. The age of onset of symptoms was 123.4 +/- 34.3 months (range: 60-168 months). Obesity was found in four (25%) of them. Two patients had venous sinus thrombosis, two had corticosteroid withdrawal, and one had posttraumatic PTC. The most common symptom was headache, recorded in 93.8% of the patients. All patients were treated medically. Two patients in our group also required a lumboperitoneal shunt. In conclusion, PTC in children is rare. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.

Pseudotumor cerebri in a child with hyperimmunoglobulin E syndrome.

Hyperimmunoglobulin E syndrome (HIES) is recognized as a multisystem disorder with various connective tissue, skeletal and immunologic abnormalities. Central nervous system abnormalities have been considered a feature of HIES. Pseudotumor cerebri (PTC) is a condition characterized by increased intracranial pressure in the absence of any intracranial mass lesion or ventricular dilatation, with normal neurology and cerebral spinal fluid composition. PTC without papilledema is rarely reported in children. We describe an atypical presentation of PTC in a child with HIES.

Cognitive functions in neurofibromatosis type 1 patients and unaffected siblings.

Attention, learning, and perceptual problems have been reported at various degrees and rates in neurofibromatosis type 1 (NF1). We aimed to define the cognitive profiles frequently associated with NF1. Children and adolescents with NF1 (n=58) were tested using Wechsler Intelligence Scales for Children-Revised (WISC-R), Judgment of Line Orientation, and Bender Visual-Motor Gestalt tests. Comparison groups were unaffected siblings of NF1 patients (n=20), children with attention deficit and hyperactivity disorder (ADHD, n=40), and normal children (n=40). No difference was found between familial or sporadic NF1 cases. Seventeen/58 (29%) of NF1 cases had a full scale IQ<70. The subgroup of NF1 patients with full scale IQ>80 (n=27) scored lower in WISC-R subtests measuring visual perception when compared to a healthy control group of similar intelligence, and lower in arithmetic but better in Bender-Gestalt and Judgment of Line Orientation tests when compared to an ADHD group of similar intelligence. These results indicate a high prevalence of mental retardation in a clinical NF1 series. NF1 patients who have normal intelligence may have impaired visual perception, but their visual perceptual problems are less than in ADHD. The tendency of unaffected siblings of NF1 patients to have mildly but consistently low test scores compared to healthy controls needs to be studied further for underlying genetic or environmental factors.

Risk factors predicting refractoriness in epileptic children with partial seizures.

The aim of this retrospective study was to determine the risk factors associated with intractability to therapy in childhood epilepsy. Fifty children with intractable epilepsy as evidenced by at least 1 epileptic fit per month were included in the study group, whereas the control group consisted of children who did not experience any recurrent seizure for at least 1 year at the time of the study. A chi( 2) test was used to evaluate the relationship between the test variables for the 2 groups, and the estimated relative risk (odds ratio) for each variable was calculated. The risk factors were subsequently determined by logistic multiple regression analysis. Univariate analysis showed that mental retardation, neurological abnormality, neuroradiological abnormality, perinatal anoxia, neonatal convulsion, presence of status epilepticus, and symptomatic etiology were significant risk factors for the development of refractory epilepsy (P < .05). For multivariate logistic regression analysis, age at seizure onset, status epilepticus, mixed type of seizures, and history of frequent seizures (more than once a month) were all found to be significant and independent risk factors for refractory epilepsy, and the number of drugs used in the study group was significantly higher than that in the control group (P < .05). In line with these findings, it was concluded that children who present with epilepsy and have these risk factors should be referred to a center where epileptic surgery is carried out without delay.

Lymphocyte subsets, TNF alpha and interleukin-4 levels in treated and untreated subacute sclerosing panencephalitis patients.

Immunologic studies in relation to clinical status might help to understand the pathogenesis of subacute sclerosing panencephalitis (SSPE) and the effect of treatment. We measured lymphocyte subsets and intracellular TNFalpha and interleukin-4 levels in peripheral blood in SSPE patients. Patients had elevated percentages of CD8+ cells compared to age-matched control children. Rapidly progressive course was associated with increased CD4+ cells. Treatment with interferons and inosiplex altered the percentage of CD3+, CD4+ and CD19+ cells. TNFalpha and interleukin-4 levels had no correlation with course or treatment. The proportions of lymphocyte subsets appear to have a role in the evolution or manifestations of SSPE, if not in the pathogenesis.

Symptomatic kidney involvement in a child with tuberous sclerosis.

Tuberous sclerosis complex is an autosomal dominant disorder of cellular proliferation and differentiation with variable penetrance and a high spontaneous mutation rate that affects multiple organs, including the kidney. Kidney involvement is commonly asymptomatic and bilateral, and rare in childhood, especially under 10 years. Herein, we report a case of unilateral renal angiomyolipoma in a nine-year-old girl with tuberous sclerosis who had symptoms of pain and macroscopic hematuria.