Assessment of tumors in children with tuberous sclerosis: a single centre's experience.

AIM: As a result of mutations in TSC1 (9q34) and TSC2 (16p13.3) tumor supressor genes, the mammalian target of the rapamycin (mTor) signaling pathway is overactivated in patients with tuberous sclerosis. Abnormal cell proliferation and differentiation is responsible for the growth several different tumors. The aim of this study was to review tumors in our patients with tuberous sclerosis. MATERIAL AND METHODS: Thirty-six patients with tuberous sclerosis were reviewed retrospectively in terms of age, sex, family history, clinical findings, presence of tumors, and treatments. RESULTS: Our study included 36 patients (18/18:M/F) aged between two days and 17 years with a median age of 6 years. There were hypopigmented spots in 30 patients, seizures in 28 patients, and a family history in 11 patients. Tumors related to tuberous sclerosis were renal angiomyolipomas in 21 patients, cardiac rhabdomyomas in 11, subependymal giant cell astrocytomas in seven, and non renal hamartoma in one patient. Everolimus treatment was used in only two patients because of hemodynamic instability. CONCLUSIONS: Tuberous sclerosis is a multisystemic disease characterized by the presence of various benign tumors and neurologic disorders. Renal angiomyolipomas, cardiac rhabdomyomas, and subependymal giant cell astrocytomas are commonly observed in patients with tuberous sclerosis. mTOR inhibitors such as everolimus and sirolimus have been increasingly used in the treatment of these tumors. However, the duration and optimal dose of mTOR inhibitors is still controversial and should be used in selected cases.

Pediatric syncope: is detailed medical history the key point for differential diagnosis?

Syncope is a transient loss of consciousness as a result of global cerebral hypoperfusion. It is generally benign but may be a sign of pathology. The purpose of this study was to analyze the frequency of syncope due to cardiac, neurocardiogenic, neurologic, situational, psychiatric, and other causes and make a differential diagnosis of syncope types according to detailed medical history and further investigations. We examined prospectively 268 children presented to pediatric polyclinics as well as cardiology and neurology departments (age range, 1-18 years) with a primary complaint of syncope for the study. Cardiac syncope was diagnosed in 12 patients, neurocardiogenic syncope in 232, neurologic syncope in 9, psychiatric syncope in 9, situational in 4, and benign paroxysmal positional vertigo in 2. The neurologic syncope group consists of patients diagnosed with epilepsy after evaluation. Eight patients in the cardiac syncope group were found to have diseases such as long QT syndrome, and the remaining patients had hypertrophic cardiomyopathy, atrioventricular nodal reentry tachycardia, ventricular tachycardia, and a second-degree heart block that can cause sudden death. In conclusion, syncope is a common problem in childhood that requires hospitalization. Because it may be the first finding of an underlying malignant cardiac or neurologic disease, clinicians must be very careful during medical evaluation. An electrocardiogram and a medical history including the details of the event, chronic diseases, and familial diseases are among the most important steps for the right diagnosis and prognosis. Instead of a routine procedure, further diagnostic workup should be directed according to medical history for high yield. Convulsive movements may be defined in all types of syncope related with cerebral hypoxia, and this may lead to a misdiagnosis of seizure by the clinician.

Pseudotumor cerebri/idiopathic intracranial hypertension in children: an experience of a tertiary care hospital.

OBJECTIVE: Pseudotumor cerebri (PTC) is diagnosed at increasing rates probably due to the increase in obesity prevalence all over the world and awareness about the disease. Our aim in this study was to evaluate the PTC clinical picture and etiological factors in children at the present time. METHOD: The records of 53 patients with 32 females, who were diagnosed with PTC in a child neurology department between the years of 2005 and 2012 were retrospectively analyzed. RESULTS: The mean age at presentation was 10.9 years (3-17 years) and approximately half of patients were aged of 11 years or less. While more than half of prepubertal patients were male, girls rate reaches 74% at puberty. An etiological factor such as venous sinus thrombosis, infections, anemia, steroid discontinuation, drugs, slit ventricle syndrome and minor head injury causing the PTC was identified in 43% of the patients. The mean duration of treatment was 6.4 months (3-24 months) and the mean follow-up duration 16.5 months (3-52 months). Visual field constriction was moderate in only two pubertal and obese female patients and mild in four patients. CONCLUSIONS: PTC is seen in prepubertal children as often as in puberty. An etiological factor causing PTC is present in about half the patients in childhood. The main etiological factors of the disease currently consist of cranial venous thrombosis, infections, anemia and drugs. Malnutrition, renutrition and related vitamin deficiencies or excesses commonly seen previously have become less important in PTC etiology. PTC is a disease that requires long-term treatment and follow-up but the prognosis is good in patients who are diagnosed early, receive appropriate treatment and show good compliance with the treatment.

Cardiac rhabdomyomas associated with tuberous sclerosis complex in 11 children: presentation to outcome.

Cardiac rhabdomyomas (CRs) are the most common heart tumors in children and closely associated with tuberous sclerosis complex (TSC). This study was performed to assess the presentation type, clinical course, treatment modalities, and outcome of the patients with rhabdomyoma, associated with TSC. We reviewed our patients with cardiac rhabdomyomas (CRs), who had received a diagnosis of TSC previously or during the follow-up period between June 1996 and January 2012, retrospectively. Thirty-two patients with TSC were evaluated and among them 11 patients (34%) were associated with CRs. Five patients (45%) had multiple tumors and consequently a total of 29 CRs were analyzed in our study. The median follow-up period was 2 years (range: 1 week-15 years). Clinical presentation was cardiac murmur in three patients, cyanosis in two patients and arrhythmia in one patient. Five patients were asymptomatic at the diagnosis and CRs were detected during routine cardiac evaluation for TSC. Cardiac tumors were diagnosed prenatally in two patients. Spontaneous regression rate was 31% and we experienced a complete regression of a tumor with an echogenic bordered tissue defect and septal thinning in a patient. Three patients had hemodynamically significant tumor obstruction; two of them underwent surgery. The other patient, who had multiple CRs, was treated medically with everolimus because of high-risk potential of surgery. Although surgical resection is the preferred treatment in most of the patients with hemodynamic instability, we need novel alternative medical therapies in some critically ill patients who cannot be operated due to various reasons.

Differences in iron deficiency anemia and mean platelet volume between children with simple and complex febrile seizures.

OBJECTIVE: The relationship between iron deficiency anemia and febrile seizures (FSs) were examined in several studies before. The aim of our study is to find out the differences regarding iron deficiency anemia, demographic characteristics and mean platelet volume (MPV) which is an inflammatory marker between simple and complex febrile seizure groups. METHODS: In this study, the authors investigated the recordings of 493 children with a diagnosis of simple and complex febrile seizure, aged between 6 months and 6 years, followed between 2002 and 2010 retrospectively. RESULTS: Mean age and male/female ratio were similar in two groups. There was no significant difference regarding with age, gender and family history of FS between two groups. We found significant difference statistically with respect to gestational age, consanguinity, family history of epilepsy and birth weight between two groups. The mean levels of Hb, Htc, MCV were lower and Plt and RDW levels were higher in children with CFS than SFS group, the differences were statistically significant (p: 0.001). A higher proportion of children with CFS (16.2%) had iron deficiency anemia compared to SFS group (12.1%). Mean platelet volume (MPV) of CFS (7.99±0.96fL) were significantly lower than that of SFS group (8.77±0.75) (p<0.001). CONCLUSIONS: The results of this study suggests that iron deficiency anemia is more frequently seen among the patients with CFS than the patients with SFS. The lower levels of MPV as an inflammatory marker, supports the idea that CFS is a brain inflammatory disease and the consequence of this inflammatory mechanism is the development of the epilepsy. Further studies are necessary to highlight the relationship between iron metabolism, inflammation and seizures.

The treatment of cerebral salt wasting with fludrocortisone in a child with lissencephaly.

Hyponatremia is the most frequent electrolyte disorder in critically ill neurological patients. The major differential diagnoses in this situation are the syndrome of inappropriate antidiuretic hormone secretion, marked by inappropriate retention of free water, and cerebral salt wasting, characterized by excessive urinary loss of sodium and resulting in polyuria and extracellular volume contraction. Cerebral salt wasting is a syndrome of hyponatremia due to increased urine output and excessive natriuresis described in patients with central nervous system disease. Although cerebral salt wasting has been well described in neurosurgical patients, data regarding pediatric patients is sparse. We present a 34-month-old boy with lissencephaly who developed cerebral salt wasting after brain biopsy. The patient was treated with hypertonic saline and multiple antiepileptic drugs. Fludrocortisone supplementation effectively treated cerebral salt wasting.

Refractive errors and strabismus in children with tuberous sclerosis: a controlled study.

PURPOSE: To evaluate the prevalence of refractive errors and strabismus in children with tuberous sclerosis and in control subjects. METHODS: Twenty-three children with tuberous sclerosis and 151 control subjects were evaluated. All children underwent cycloplegic autorefraction or retinoscopy, slit-lamp biomicroscopy, and dilated fundus examination. Ocular alignment was assessed by the Hirschberg, Krimsky, or prism cover test. RESULTS: The total prevalence of hypermetropia and amblyopia was significantly higher in patients with tuberous sclerosis (P = .035) than in the control subjects (P = .002). CONCLUSION: A high prevalence of hypermetropia seems to be an additional feature of tuberous sclerosis. Early screening for this amblyogenic factor is indicated in patients with tuberous sclerosis.

Hypomelanosis of Ito and Sturge-Weber syndrome without facial nevus: an association or a new syndrome?

Sturge-Weber syndrome without facial nevus is rare. Twenty-four cases were previously reported. Although hypomelanosis of Ito is a relatively common disorder, there was only one previous case in association with Sturge-Weber syndrome. We describe an 11-year-old boy with Sturge-Weber syndrome without facial nevus, coexistent with hypomelanosis of Ito.

Refractive errors in neurofibromatosis type 1 and type 2.

OBJECTIVE: To document the prevalence of refractive errors in patients with neurofibromatosis type 1 (NF1) and type 2 (NF2) and to compare it with that of age- and sex-matched controls. METHODS: 82 patients with NF1, 21 patients with NF2 and 103 age- and sex-matched controls were evaluated in this prospective observational case-control study. Cycloplegic autorefraction and dilated fundus examination were performed. Myopia was defined as the spherical equivalent refraction of at least -0.50 diopters (D), hyperopia as the spherical equivalent refraction of at least 2.0 D and astigmatism as the cylinder of at least 1.0 D. Main outcome measures were refractive error, IQ, years of education, height, weight and body mass index (BMI). RESULTS: The prevalence of myopia was 23.1% in patients with NF1, 23.8% in patients with NF2 and 16.5% in age- and sex-matched controls. These differences were significant (p<0.03, p<0.03), and adjusting for intelligence, education, height, weight and BMI increased the significance of this finding (p<0.001, p<0.001). The prevalences of astigmatism and hyperopia were similar in both groups. CONCLUSION: A high prevalence of myopia seems to be an additional feature of NF1 and NF2.

Serological follow-up in juvenile myasthenia: clinical and acetylcholine receptor antibody status of patients followed for at least 2 years.

Thirty cases of juvenile myasthenia with at least 2 years' follow-up and one measurement of acetylcholine receptor antibody titer were evaluated. Symptoms were initially ocular in 15 (50%) cases; only one developed generalized disease and others remained ocular in 2-24 years' follow-up. Antibodies to acetylcholine receptor (AchRAb) were absent in 12/30 (40%) of all patients initially, but became positive in 5/28 (18%) on further testing in 1-5 years. Spontaneous remission was observed in 6 cases (20%) of whom one became seropositive, and late relapses after 5-11 years' remission were observed in 3 patients with ocular myasthenia, of whom only one developed AchRAbs. Our results show ocular JM has an exceptional tendency to remain confined to these muscles, and delaying the classification of the disease as AchRAb-negative for a few years and repeating serological tests is advisable in the follow-up.