Yılmaz Ay

Neuropsychologic Impairment in Children With Rolandic Epilepsy

Although patients with benign childhood epilepsy with centrotemporal spikes exhibit normal intelligence, they frequently display neuropsychologic abnormalities. Thirty-five patients with rolandic epilepsy were included in this study. They were divided into three subgroups. Group I comprised patients with rolandic focus who were not receiving treatment. Group II comprised patients with rolandic focus who were receiving treatment. Group III comprised patients who demonstrated improved foci and were not receiving treatment. The control group comprised 16 children who were similar to patients in terms of age, sex, and sociocultural level. All children underwent standardized neuropsychologic testing, including the Wechsler Intelligence Scale for Children-Revised subtests, Bender Gestalt Test, Stroop Test, Visual Aural Digit Span, Reading and Writing Performance, and Dichotic Listening Test. Patients exhibited significantly impaired visuomotor and reading ability and attention to verbal stimuli compared with control subjects. Reading disability persisted in patients in remission from seizures and epileptic discharges. Contrary to the presumed benign nature of rolandic epilepsy, this disorder may cause learning disabilities. Therefore, patients must be followed longitudinally to identify any learning problems.

A rescue therapy with a combination of caspofungin and liposomal amphotericin B or voriconazole in children with haematological malignancy and refractory invasive fungal infections.

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5–17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3–69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the combination was switched to caspofungin + voriconazole. The median (range) and total duration of the therapy were 7 (3–14) days and 91 patient days for LAmB + caspofungin combination and 49 (7–126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable response rate of 68.4% in 16 proven or probable IFI episodes. Twelve‐week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies.

Long-term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia

Summary.  Radioisotope synovectomy (RS) is defined as the intra‐articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium90 (Y90) and Rhenium186 (Re186) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 ± 6.2 years (range: 8–40). Y90 was used for knees, Re186 was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y90 and Re186 does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re‐evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

Experience of Pandemic Influenza with H1N1 in Children with Leukemia

It is not exactly known the risks from infection with pandemic influenza (H1N1) 2009 in children with leukemia. Here the authors present their experience in 5 children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16 years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblasic leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2 patients were receiving intensive chemotherapy. All patients had fever, rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1 revealed respiratory distress. Stomachache and diarrhea was seen in the patient who had no pneumonia. All treated as inpatients, but none of them required hospitalization in intensive care unit. One to 3 days after the symptoms of influenza appeared, oseltamivir (Tamiflu) was given to all patients in combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1 to 3 days after treatment was started. The patients received oseltamivir for 5 to 7 days. Cell culture tests were found to be positive for influenza A and polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be very dangerous for children with leukemia if the oseltamivir treatment was given early when symptoms of influenza appeared.

An evaluation of the DDAVP infusion test with PFA-100 and vWF activity assays to distinguish vWD types in children.

von Willebrand disease (vWD) is classified into partial (type 1), qualitative (type 2), and total deficiency (type 3).The aims of the study were to evaluate prospectively the potency of the DDAVP infusion test together with von Willebrand factor (vWF) ristocetin cofactor (vWF:RCo), vWF antigen (vWF:Ag), factor VIII coagulant activity (FVIII:C), and platelet function analyzer (PFA)-100 to distinguish vWD types. Genetic analysis and multimeric analysis of vWF was not applied. We classified the 112 patients and 47 healthy children phenotypically according to the laboratory test results and bleeding severity score. PFA-100 closure times (CT), FVIII:C, vWF:RCo, vWF:Ag, ristocetin-induced platelet aggregation (RIPA), and the response of FVIII:C and vWF parameters to desmopressin (DDAVP) were used to define types 1, 2, and 3 vWD. Type 1 vWD is mild in 34 cases (vWF:RCo % 40-55), moderate in 29 (vWF:RCo %27-40), severe type 1 vWD or nonclassical type 2 vWD in 12 cases (vWF:RCo % 4-16), and type 2 vWD in 23 cases (vWF:RCo %4-38).The response to DDAVP of vWF parameters is normal in all patients with mild/moderate type 1 vWD, 6 patients with severe type 1 vWD or nonclassical type 2 vWD and 11 patients with type 2 vWD. In conclusion, this study showed that measurement of vWF:RCo, vWF:Ag, FVIII:C, and PFA-100 parameters can differentiate vWD types but not severe type 1 vWD or nonclassical type 2 vWD. In the differentiation of severe type 1 vWD and nonclassical type 2 vWD, DDAVP response may be used.

Rabbit Antithymocyte Globulin Treatment in Childhood Acquired Severe Aplastic Anemia

Acquired severe aplastic anemia (SAA) is a life threatening bone marrow failure characterized by pancytopenia and hypocellular bone marrow. Matched sibling donor is not available for majority of the patients and many children receive immunosuppressive therapy (IST). Although horse antithymocyte globuline (ATG) is the preferred option, our patients received rabbit ATG; since horse ATG is not available in Turkey. We reviewed the medical records of children with SAA who were treated with rabbit ATG, cyclosporine, and granulocyte colony stimulating factor (GCSF) between 2006 and 2012. Fifteen children with SAA aged between 1.5 and 17 years received rabbit ATG as first line treatment. Only two of them showed partial response and the others did not give any response at 3rd, 6th, and 12th months after the first course of IST. The second course of ATG was given to 8 of the patients; Rabbit ATG at the same dosage was used for 3 of them, and others were given horse ATG. None of the patients responded to the second course of ATG. Invasive fungal infection (IFI) which was seen in 80% of the patients was the most significant problem. Overall survival rate was 60%. The median time between the diagnosis and initiation of IST was 57 (range; 29–144) days. This delay might be significantly contributed to unresponsiveness. In our series, the use of rabbit ATG was not effective for these patients as first line treatment modality. Response rate was very low and the incidence of fungal infections was very high in the SAA patients who received rabbit ATG.

Leukapheresis in Childhood Acute Leukemias: Single-Center Experience

Hyperleukocytosis in patients with leukemia is associated with early mortality, especially due to the pulmonary and neurological complications of leukostasis. The prompt use of leukapheresis may improve patients’ survival in the initial treatment period. The medical records of all previously untreated acute leukemia patients were reviewed to determine whether there was hyperleukocytosis at presentation. This study summarizes a single-center experience of leukapheresis that was applied to 12 children with acute leukemia and hyperleukocytosis. The median leukocyte count at diagnosis was 589,000/mm3 (range: 389,000–942,000/mm3) for ALL patients and 232,000/mm3 (range: 200,000–282,000/mm3) for AML patients. A central venous catheter (CVC) was inserted, and leukapheresis procedures were repeated at 12-hour intervals. A total of 29 leukapheresis cycles were performed on 12 children. The median number of cycles of leukapheresis required by each patient was two (range: 1–4). The median absolute and percentage reductions in white blood cell (WBC) count after the first cycle of leukapheresis were 113,000/mm3 (range: 55,000–442,000/mm3) and 36% (range: 16–57.4%), respectively. As a laboratory finding, mild hypocalcemia was the most frequently observed complication. No patients developed any other problem related to the procedure. Our results showed that leukapheresis is a safe and effective procedure if performed by experienced staff.

Hemophagocytic lymphohistiocytosis associated with H1N1 virus infection and visceral leishmaniasis in a 4.5-month-old infant

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

Central Core Disease: Atypical Case With Respiratory Insufficiency in an Intensive Care Unit:

Central core disease is a rare congential myopathy characterized by formation of typical cores in myofibrils. We report an atypical case of central core disease with respiratory insufficiency in the late stage of congenital myopathy. A 13-year-old girl was admitted to the intensive care unit with the diagnosis of respiratory distress syndrome. Ventilatory support was initiated. After 2 weeks of follow-up, the Division of Pediatric Neurology was consulted owing to the failure to wean her from the ventilator. Clinical and electromyographic features were in favor of primary muscle disease. Muscle biopsy revealed typical cores in type 1 muscle fibers, which were diagnostic for central core disease. This case was presented to emphasize that patients with respiratory distress who cannot be weaned from the ventilator should be evaluated for central core disease with an atypical presentation. (J Child Neurol 2006;21:173—174; DOI 10.2310/7010.2006.00031).

Resemblance to vWD types and laboratory diagnosis of obligatory carriers of type 3 von Willebrand disease.

Objectives: It is important to diagnose obligatory carrier (OC) type 3 von Willebrand Disease (vWD) in countries, such as Turkey, where marriages between relatives is common. However, mild bleeding or no bleeding in such patients complicates the diagnosis of the disease. It is not clear how the diagnosis of OC type 3 vWD will be made based on FVIII:C (Factor VIII activity), vWF:Ag (von Willebrand factor antigen), vWF:RCo (von Willebrand factor ristocetin cofactor activity), and PFA (platelet function analyzer )-100 parameters. Therefore, the purpose of the study is to investigate how OC type 3 vWD diagnoses may be established by studying laboratory phenotypes of close relatives of patients with diagnosed 3 vWD. Patients and Methods: 8 patients with type 3 vWD (index cases) and 20 patients who were defined as OCs type 3 vWD were enrolled into the study. Result: 10 cases had similarity with mild type VWD, 4 cases had similarity with moderate type 1 vWD, 4 other cases had type 1 or 2 vWD similarities, 1 case had similarity with severe type 1 vWD, and 1 case also had similarity with severe type 1 or type 2 vWD; regarding their laboratory phenotypic characteristics. Conclusion: we identified that OC type 3 vWD is similar specifically to type 1 vWD in terms of laboratory phenotypic character, and we suggest that it may be used with PFA-100 as an easy and fast method in screening relatives.