[The role of zonisamide in the management of pediatric partial epilepsy]. / A zonisamid szerepe a gyermekkori fokális epilepszia gyógyszeres kezelésében.

In our review we discuss the group of approved antiepileptic drugs for children in Hungary. We cite the results of the review conducted by the International League Against Epilepsy on antiepileptic drug efficacy and effectiveness as initial monotherapy for newly diagnosed epileptic seizures and syndromes in pediatric age group. 25% of pediatric epilepsy is therapy resistant, so we further need new drugs, which must be investigated according to the rules of the European Medicine Agency. The ethical dilemmas of childhood drug studies lead to the situation that the new antiepileptic drugs, approved as monotherapy in adult epilepsies, are in the majority just in add-on regimen tested in pediatric patients. As clinicians we appreciate open label extension safety studies. An old-new antiepileptic drug in Europe is zonisamide. Though it was approved for first line monotherapy in pediatric and adult patients with partial and generalised epilepsy in 1989 in Japan, the European Medicine Agency licensed its use as adjunctive therapy in children aged 6 years or older with partial seizures (with or without secondary generalisation) just in 2013. The results of the openlabel extension study appeared in 2014. The mean dose received was 7.5 mg/kg/day. During the open label phase 11% of the patients achieved seizure freedom and it was maintained throughout the study. The drug was generally well tolerated. The most frequently reported treatment-related adverse events were decreased weight (6%), decreased appetite (4%), and headache (2%). No new or unexpected side effects emerged. In conclusion oral zonisamide as adjunctive therapy in pediatric patients aged 6-17 years with partial seizures demonstrated an acceptable safety and tolerability profile and efficacy over a period at least 1 year. So it is a good treatment option in this population.

Visual and neurologic deterioration in otogenic lateral sinus thrombosis: 15 year experience.

OBJECTIVES: Otogenic lateral sinus thrombosis is a rare complication of acute otitis media whose clinical presentation has changed with the early use of antibiotics. The aim of this study was to analyze the changing clinical signs, vaccination status, therapeutic management and outcome of these patients. METHODS: Retrospective chart review of 10 children treated with otogenic lateral sinus thrombosis in a tertiary level teaching hospital in Budapest, Hungary, from January 1998 till August 2013. RESULTS: Patients were divided into Early and Late presenting groups. In the Early presenting group, sepsis developed within one week after the onset of acute otitis media. At admission otological symptoms were predominant. The Late presenting group experienced acute otitis media several weeks prior to presentation and in this group neurologic symptoms dominated the clinical picture at admission. All patients received antibiotics. Eight of them were also treated with low molecular weight heparin. All children underwent cortical mastoidectomy. After surgery, the clinical signs of elevated intracranial pressure transiently worsened. This manifested as progression of papilledema in seven children, causing severe visual disturbance in two cases. After medical treatment and serial lumbar punctures all patients except one recovered. This child has permanent visual acuity failure of 0.5D unilaterally. At one year follow up complete and partial recanalization were noted in five and two patients, respectively. CONCLUSIONS: After mastoidectomy the signs of elevated intracranial pressure can transiently worsen, papilledema can progress. Daily bedside monitoring of visual acuity and regular ophthalmoscopy with neurologic examination is recommended during hospitalization. Close follow up is advised up to one year. When the dominant sinus is occluded, the clinical scenario is more protracted and severe.

Timely recanalization of lateral sinus thrombosis in children: should we consider hypoplasia of contralateral sinuses in treatment planning?

The objective of this study was to evaluate long-term clinical and radiological outcomes in children treated with lateral sinus thrombosis secondary to acute mastoiditis considering also contralateral sinus hypoplasia. This study was a retrospective chart review, conducted in tertiary pediatric hospital. Medical reports of eight children with acute mastoiditis and lateral sinus thrombosis from 1998 to 2011 were examined in terms of therapy, clinical recovery and radiological proof of lateral sinus recanalization. Three children presented hypoplasia of contralateral venous drainage system. Condition of sinuses was regularly monitored with MRI. Otologically and neurologically, all children recovered fully. All received antibiotics; six received additional low molecular weight heparin therapy. Mastoidectomy was performed on six cases. Incision and thrombectomy were applied in the other two, one involving internal jugular vein ligation. This latter case presented also contralateral venous hypoplasia; visual impairment proved permanent. The other two children with contralateral sinus hypoplasia recovered fully after steroid, dehydration and low molecular weight heparin therapy. Recanalization occurred in all children except the one with internal jugular vein ligation, in whom good collateral circulation was observed. There were no bleeding complications. Anatomical variations of cerebral venous drainage system can frequently be observed and should be considered in treatment planning. Mastoidectomy with antibiotics and additional low molecular weight heparin treatment is a safe, promising alternative to thrombectomy and internal jugular vein ligation in children with lateral sinus thrombosis following acute mastoiditis, also having contralateral sinus hypoplasia. Recanalization can be expected within two to five months.

[Guillain-Barré syndrome in childhood]. / Guillain-Barré-szindróma gyermekkorban.

BACKGROUND: Guillain-Barré syndrome (GBS) is clinically well known since 1916. It can occur at any age. Its main characteristic is acute rapidly ascending flaccid paresis. It is a neuro-immunologic disorder with heterogeneous background. In Hungary we could not find reports about big paediatric population with GBS. PATIENT AND METHOD: We analysed retrospectively the data of 38 children diagnosed and treated with GBS at the Neurological Department of Paul Heim Children's Hospital or at the Paediatric Department of St. László Hospital from January 2000 till April 2008. We analysed the clinical characteristics, seriousness of clinical signs, laboratory results, and electrophysiological features of them as well documented the preceding illness. We observed the effectiveness of our treatment; we measured the speed and time of the healing process and documented the residual clinical signs. RESULTS: 35 children could be classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 2 as having acute motor axonal neuropathy (AMAN) and 1 as Miller-Fisher syndrome. By those patients who at the very beginning did not show the characteristic clinical signs, electrophysiology helped in establishing the diagnosis. By one child spinal MRI with gadolinium supported our diagnosis. Those children, who lost their ambulation, got immunotherapy: intravenous immunoglobulin (IVIG) or plasmapheresis (PEX). Both method seemed to be effective. None of our patients died. All were cured. By five patients residual clinical symptoms could be found. CONCLUSION: The disease process, the relative incidence of each subtype of GBS is nearly similar to that in Western Europe and North America according to the literature. By the currently used immune therapy most of the pediatric patients recover fully within a short time.

[Acute transverse myelitis in childhood]. / Akut myelitis transversa gyermekkorban.

We reviewed the medical history, clinical signs, imaging studies, laboratory data and treatment effectiveness of our 10 patients presented with acute idiopathic transverse myelitis. We used the criteria of the Transverse Myelitis Consortium Working Group (2002). So we excluded all those cases by whom the cause of the inflammation could be detected (e. g. direct viral inflammatory disease, systemic autoimmune disease). Age of the patients at disease onset ranged from 3 to 15 years. The first clinical signs were pain in different locations, and urinary retention. Paraparesis or plegia reached its maximum within five days. By all patients spinal MRI and lumbar puncture were performed at admission. These results were interpreted together with the clinical signs, and therapy was started immediately. We used methylprednisolon pulse therapy. Within 10-30 days the patients started to walk. We have followed the children for 1.5-13 years. Few residual clinical signs were observed: by one child left sided spastic monoparesis persisted, by the other right sided latent monoparesis was stated, and by one partial urinary incontinence persisted. By the control spinal MRI persisting signal changes or atrophy were detected just by those two children who had residual clinical signs. In the follow-up period no clinical relapse occured. Neither did the brain or spinal MRI show new lesions. The quick diagnosis and the immediately started therapy determine mostly the clinical outcome of these children. We hope that our long follow-up period can help in better understanding the disease even in adult patients. In the future we try to join multicenter clinical studies.

[Severe intracranial hypotension in an adolescent with Marfan syndrome. Case report]. / Súlyos fokú spontán intracranialis hipotenzió Marfan-szindrómás serdülô esetében.

Spontaneous intracranial hypotension is a rare complication of connective tissue disorders. One of them is Marfan syndrome. It predisposes the patient to meningeal diverticula. Possibly after minor unrecognised head trauma or secondary to Valsalva manoeuvre cerebrospinal fluid leak from meningeal diverticula can happen. It causes postural headache. We describe a 15 year old adolescent female newly diagnosed with Marfan syndrome, who presented with intractable postural headache. Our patient's brain MRI showed bilateral frontal subdural effusion, narrow ventricles, downward displacement of the brainstem, enlarged cervical venous plexi, dural ectasias and wide nerve root sleeves. Radionuclide cisternography demonstrated CSF leaks at multiple sites. She could not be treated conservatively, but was successfully treated by epidural saline injections. Control brain and cervical MRI confirmed her healing, too. At the two and half year follow up visit, she was completely well. So we recommend this easy technique to be used before epidural autologous blood patches.

[Experience with levetiracetam in childhood epilepsy]. / Tapasztalatok a levetiracetamkezeléssel gyermekkori epilepsziákban.

OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam in children with drug resistant epilepsy from a retrospective study. METHODS: We report the result of a study of 85 pediatric patients (mean 10.5 years, range: 1-24) with refractory generalized and focal epilepsy, who received levetiracetam as add-on treatment. The average duration of epilepsy was eight years, and the patient were treated with mean of 6.0 antiepileptic drugs before levetiracetam was introduced. RESULTS: Ten patients (12%) became seizure-free, three (3%) responded with seizure reduction of more than 90%, 32 (38%) responded with seizure reduction of more than 50% following introduction of levetiracetam. No response to levetiracetam was reported in 34% (n: 29). Positive psychotropic effect was observed in 26 patient (30%). Mild to moderate side effects were reported in 11 patients (13%), consisting most frequently general behavioral changes, aggression, sleep disturbances, but they ceased after decreasing the dose of levetiracetam. Mental retardation was associated with poor response and associated with more side effects. CONCLUSION: Levetiracetam is a well tolerated new antiepileptic drug that may effectively improve seizures control as an add-on drug in resistant epilepsy in childhood with good tolerability.

Quantitative EEG effects of carbamazepine, oxcarbazepine, valproate, lamotrigine, and possible clinical relevance of the findings.

UNLABELLED: Quantitative EEG (QEEG) effects of therapeutic doses of carbamazepine (CBZ), oxcarbazepine (OXC), valproate (VA) and lamotrigine (LA) monotherapy were investigated in patients with beginning epilepsy. Baseline waking EEG (EEG1) was recorded in the untreated state, the second EEG (EEG2) was done after 8 weeks of reaching the therapeutic dose. Left occipital data were used for analysis. QEEG target parameters were absolute band-power (delta: AD, theta: AT, alpha: AA, beta: AB), and alpha mean frequency (AMF). Group effects (untreated versus treated condition in the CBZ, VA, OXC, LA groups) were computed for each target parameter. One group with benign rolandic epilepsy remained untreated for clinical reasons and served to estimate the QEEG test-retest differences. In addition, the individual QEEG response to each drug was calculated as (EEG2-EEG1). RESULTS: statistically significant (p<0.05) group differences indicated the QEEG domain systematically affected by the drugs. CBZ caused AT increase and AMF decrease. OXC caused AMF decrease. VA and LA did not decrease AMF (LA even increased it), but reduced broad-band power. Individual power and AMF changes showed considerable variability in each group. >0.5 Hz AMF decrease (that was reported to predict cognitive impairment in prior studies) occurred in 10/41 patients in the CBZ group but never in the OXC, VA, LA groups. The results may be utilized in planning further studies addressing the relationship between antiepileptic drugs and their CNS effects. In addition, the relationship of AED-related cognitive impairment and AMF changes was discussed.

[Neurologic aspects of HIV infections--follow-up of pediatric patients]. / A HIV-fertózés neurológiai vonatkozásai. Gyermek betegek követésének tapasztalatai.

OBJECTIVES: Before the widespread introduction of combined antiretroviral therapy (1995) complications from HIV and AIDS in the central nervous system had been reported in larger proportion in infants and children than in adults: 80-90% versus 60-70%. Particular clinical manifestations tend to occur at different stages during the evolution of HIV infection. The authors review the neurological aspects of HIV infection. METHOD: First, a summary of the protocol of the neurological examinations and related experience is given. Then authors present the evaluation of neuro-psychological development, prevalence of neurological impairment and neuro-imaging of nine HIV infected children (seven boys, two girls) for the period of ten years (1991-2001). Three/ten children had vertically transmitted HIV six/nine were infected by a nosocomial route in their early childhood. Children were regularly followed up from the diagnosis of HIV. The median follow up time has been 79 month (range: 18-144 month). Four patients died during the study period. The neurological status, the motor and mental development were examined at three month intervals or monthly under one year of age. EEG was performed every six month and CT/MRI once a year. All patients received combined antiretroviral treatment and immunoglobulin therapy continuously. RESULTS: Three/nine children have normal development, one/nine has hyperactive and attention deficit disorder with normal IQ range, two/nine have slight, one/nine moderate and two/nine serious mental retardation. Mild neurological signs were found in two children, various moderate and serious neuro/psychological symptoms were found in four patients, one of them was treated with benign epilepsy too. There was also dose correlation between the clinical symptoms and the results of EEG examination (diffuse background slowing) and results of neuroimaging studies (cortical atrophy, calcification of the basal ganglia, toxoplasma abscesses). According to the results of different examinations three/nine children were found to be symptom-free, one/nine case showed the static form, two/nine patients showed the plateau form, two/nine the rapid progressive form and one/nine the progressive infantile form of AIDS encephalopathy. The majority of the patients suffered from adopting problems and difficulties of socialisation since their families lives were damaged by isolation and rejection from the community. CONCLUSION: The regular neurological and psychological examinations completed with EEG, CT/MRI were very informative to follow the course of neuro-psychological problems of HIV infected children. Symptom-free patients have to face psychosocial problems too, which cause much more damage in their mental progress than HIV itself.

Virological, Neurological and Histological Investigations of a Child Born to a Mother with AIDS.

HIV-1 was isolated from a child at 6 and 9 months of age, proving the vertical transmission of infection from the mother with AIDS. The p24 antigen test of the plasma at 9 months of age was positive as well. A positive PCR reaction was detected in J34 cells, infected with the supernatant of the peripheral blood lymphocytes of the child. According to phenotypic characterization, the virus proved to be a SI (syncytium inducing) isolate, growing in PBL, MT2, J34 and other T and monocytic cell lines. The isolate was AZT sensitive. Two methods were applied for genotypic characterization: 1. Heteroduplex mobility assay (HMA), 2. Sequence analysis of a part of the env gene. On the basis of both of these methods, this virus belongs to the B subtype of HIV-1, which is prevalent mainly in Europe and in the USA. The neurological status of the child was followed regularly. At autopsy the presence of p24 antigen was detected in glial cells of the frontal cortex, proving the presence of the virus in the brain. A retardation of the development of the central nervous system could be observed as well.