Katalin Hollódy

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.

Staged bilateral stereotactic pallidothalamotomy for life-threatening dystonia in a child with Hallervorden–Spatz disease

Hallervorden–Spatz disease (HSD) is a rare disorder characterized by progressive motor dysfunction and dementia. Dystonia is the most prominent and disabling symptom, responding only to a modest extent to pharmacological therapy. At the moment, only a few cases have been reported to improve dystonia and even fewer to resolve status dystonicus for a longer period in children. The authors present the case of a 10‐year‐old boy who had progressive generalized dystonia, resulting in spontaneous femur fracture and life‐threatening swallowing and respiratory disability. As a rescue solution, staged bilateral pallidothalamotomy was performed. Postoperatively, Burke–Fahn–Marsden Dystonia Rating Scale and Dystonia Disability Rating Scale improved (from 116 and 30 points to 41 and 18 points, respectively) and painful dystonia was resolved, which was still continuous 4 years later (47 and 20 points). Stereotactic staged bilateral pallidothalamotomy should be considered as a potential treatment in the management of life‐threatening generalized dystonia related to HSD.

Does vigabatrin treatment for infantile spasms cause visual field defects? An international multicentre study.

The aim of this study was to examine whether vigabatrin treatment had caused visual field defects (VFDs) in children of school age who had received the drug in infancy.

Mitochondrial dysfunction and organic aciduria in five patients carrying mutations in the Ras-MAPK pathway

Various syndromes of the Ras-mitogen-activated protein kinase (MAPK) pathway, including the Noonan, Cardio-Facio-Cutaneous, LEOPARD and Costello syndromes, share the common features of craniofacial dysmorphisms, heart defect and short stature. In a subgroup of patients, severe muscle hypotonia, central nervous system involvement and failure to thrive occur as well. In this study we report on five children diagnosed initially with classic metabolic and clinical symptoms of an oxidative phosphorylation disorder. Later in the course of the disease, the children presented with characteristic features of Ras-MAPK pathway-related syndromes, leading to the reevaluation of the initial diagnosis. In the five patients, in addition to the oxidative phosphorylation disorder, disease-causing mutations were detected in the Ras-MAPK pathway. Three of the patients also carried a second, mitochondrial genetic alteration, which was asymptomatically present in their healthy relatives. Did we miss the correct diagnosis in the first place or is mitochondrial dysfunction directly related to Ras-MAPK pathway defects? The Ras-MAPK pathway is known to have various targets, including proteins in the mitochondrial membrane influencing mitochondrial morphology and dynamics. Prospective screening of 18 patients with various Ras-MAPK pathway defects detected biochemical signs of disturbed oxidative phosphorylation in three additional children. We concluded that only a specific, metabolically vulnerable sub-population of patients with Ras-MAPK pathway mutations presents with mitochondrial dysfunction and a more severe, early-onset disease. We postulate that patients with Ras-MAPK mutations have an increased susceptibility, but a second metabolic hit is needed to cause the clinical manifestation of mitochondrial dysfunction.

Theta EEG source localization using LORETA in partial epilepsy patients with and without medication

OBJECTIVE To investigate and localize the sources of spontaneous, scalp-recorded theta activity in patients with partial epilepsy (PE). METHODS Nine patients with beginning, untreated PE (Group 1), 31 patients with already treated PE (Group 2), and 14 healthy persons were investigated by means of spectral analysis and LORETA, low resolution electromagnetic tomography (1 Hz very narrow band analysis, age-adjusted, Z-scored values). The frequency of main interest was 4-8 Hz. RESULTS Group analysis: Group 1 displayed bilateral theta maxima in the temporal theta area (TTA), parietal theta area (PTA), and frontal theta area (FTA). In Group 2, theta activity increased all over the scalp as compared to the normative mean (Z=0) and also to Group 1. Maximum activity was found in the TTA, PTA, and FTA. However, in the PTA and FTA the centers of the abnormality shifted towards the medial cortex. Individual analysis: all the patients showed preferential activation (maximum Z-values) within one of the three theta areas. CONCLUSIONS EEG activity in the theta band is increased in anatomically meaningful patterns in PE patients, which differs from the anatomical distribution of theta in healthy persons. SIGNIFICANCE The findings contribute to our understanding of the sources of theta rhythms and the pathophysiology of PE.

MRI classification system (MRICS) for children with cerebral palsy: development, reliability, and recommendations

To develop and evaluate a classification system for magnetic resonance imaging (MRI) findings of children with cerebral palsy (CP) that can be used in CP registers.

Valproate treatment normalizes EEG functional connectivity in successfully treated idiopathic generalized epilepsy patients

AIM To investigate the effect of chronic VPA treatment of EEG functional connectivity in successfully treated idiopathic generalized epilepsy (IGE) patients. PATIENTS AND METHODS 19-channel waking, resting-state EEG records of 26 IGE patients were analyzed before treatment (IGE) and after the 90th day of treatment (VPA), in seizure-free condition. Three minutes of artifact-free EEG background activity (without epileptiform potentials) was analyzed for each patient in both conditions. A group of 26 age-matched healthy normative control persons (NC) was analyzed in the same way. All the EEG samples were processed to LORETA (Low Resolution Electromagnetic Tomography) to localize multiple distributed sources of EEG activity. Current source density time series were generated for 33 regions of interest (ROI) in each hemisphere for four frequency bands. Pearson correlation coefficients (R) were computed between all ROIs in each hemisphere, for four bands across the investigated samples. R values corresponded to intrahemispheric, cortico-cortical functional EEG connectivity (EEGfC). Group and condition differences were analyzed by statistical parametric network method. MAIN RESULTS p<0.05, corrected for multiple comparisons: (1) The untreated IGE group showed increased EEGfC in the delta and theta bands, and decreased EEGfC in the alpha band (as compared to the NC group); (2) VPA treatment normalized EEGfC in the delta, theta and alpha bands; and (3) degree of normalization depended on frequency band and cortical region. CONCLUSIONS VPA treatment normalizes EEGfC in IGE patients.

Trends in prevalence and characteristics of post-neonatal cerebral palsy cases: a European registry-based study.

The present paper aims to analyze trends over time in prevalence of cerebral palsy of post-neonatal origin, to investigate whether changes are similar according to severity and to describe the disability profile by etiology. Post-neonatal cases, birth years 1976 to 1998, were identified from the Surveillance of Cerebral Palsy in Europe collaboration (19 population-based registries). A recognized causal event occurring between 28 days and 24 months of age was considered to define the cases. Trends in prevalence were explored using graphical methods (Lowess and Cusum control chart) and modeled with negative binomial regressions. Over the study period, 404 cases were identified as post-neonatal cases (5.5% of the total). Mean prevalence rate was 1.20 per 10,000 live births (95% CI [1.08-1.31]). A significant downward trend was observed (p=0.001), with an accentuated decrease in the 1990 s. The prevalence of severe cases which account for around one third of the total also significantly decreased over time (p<0.001). In 46% of cases, an infectious aetiology was reported; the corresponding prevalence significantly decreased since 1989. No significant decrease was observed for the rate of cases due to a vascular episode or of traumatic origin. Our results emphasize the need of large population-based surveillance systems to reliably monitor trends in prevalence in rare subgroups of children like those with acquired cerebral palsy. The decrease of the overall prevalence as well as those of the most severe cases may be partly due to public health actions targeted to prevent such events.

EEG functional connectivity of the intrahemispheric cortico-cortical network of idiopathic generalized epilepsy.

AIMS Intrahemispheric, cortico-cortical EEG functional connectivity (fC) was investigated in untreated patients with idiopathic generalized epilepsy (IGE) in this explorative study. PATIENTS AND METHODS Group comparison was carried out between 19, drug-naive IGE patients and 19, matched healthy persons. 90×2s of 19 channels waking, interictal background EEG signal (without epileptiform potentials) were processed to the LORETA (low resolution electromagnetic tomography) software to compute current source density for 2394 voxels representing parcels of the cerebral cortex for 25 very narrow bands of 1Hz bandwidth (VNBs) from 1 to 25Hz. EEG fC was investigated among the already localized sources. Pearson correlation coefficients (R) were computed among the 33 regions of interest (ROI) within the left and within the right hemisphere, separately. Group differences were computed by means of t-statistics. Corrected p<0.05 differences were accepted as statistically significant. MAIN RESULTS (1) The anatomical patterns of the fC differences showed great frequency-dependency. (2) Hemispheric asymmetry was prominent within most VNBs. (3) Decreased fC in the IGE group was found across all VNBs in the 1-6Hz frequency range as compared to mixed patterns comprising both increased and decreased fC at >6Hz frequencies. (4) In the 5-25Hz range, decreased fC dominated in the anterior, increased fC in the posterior parts of the cortex. (5) The results delineated an anterior and a posterior network. DISCUSSION (1) Decreased fC in the 1-6Hz band might indicate some relationship to yet hidden structure network abnormalities. (2) The anatomical patterns of fC indicate frequency-dependent, pathological coupling and decoupling processes in the interictal state. (3) The two networks might help to understand seizure liability and seizure precipitation in IGE. SIGNIFICANCE This is the first study to explore EEG fC in the interictal condition of IGE patients. The importance of EEG frequencies in evaluating fC in IGE was demonstrated and starting points for further research were given.

Transverse Myelitis as a Rare, Serious Complication of Mycoplasma pneumoniae Infection

We report on the first published case of a Mycoplasma pneumoniae-associated transverse myelitis appearing in childhood and leading to persistent paraplegia and bowel and bladder dysfunctions. Magnetic resonance imaging of the spinal cord indicated extensive transverse myelitis extending from T(5)-T(12). A repeated scan established spinal cord atrophy in the affected area. Various therapies (methylprednisolone pulse therapy, plasmapheresis, and roxythromycine) produced no clinical effect.