Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. Methods: We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. Results: We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Discussion and conclusion: Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Resective Epilepsy Surgery and Respective Histopathological Diagnoses: A Retrospective Cohort Study.

INTRODUCTION: Over recent decades, brain resection for drug-resistant epilepsy has proven to be a valuable treatment option. The histopathological classification was of paramount value for patient management. The aims of this study were to characterize our resective epilepsy surgical series including the histopathological diagnoses and to understand the differences in clinical practice between two different periods of our epilepsy surgical programme. MATERIAL AND METHODS: We performed a retrospective cohort study, including patients with drug-resistant epilepsy that underwent resective surgery between 1997 and 2021 in the Coimbra University Hospital Centre. Histopathological diagnoses were classified into seven major conventional categories. For comparison purposes, the cohort was divided into two consecutive periods of 12 years. RESULTS: A total of 259 patients were included, from which 228 (88%) were adults at the time of surgery. The median disease duration prior to surgery was 14 (interquartile range 23) years. Fifty-five (21%) patients performed pre-surgical invasive work-up. The temporal lobe was the most frequently operated region (73%). Major and minor post-surgical complications were identified in 21 (8%) patients. A reduction in the number of antiepileptic drugs was possible in 96 (37%) patients after surgery. The most common histopathological diagnosis was hippocampal sclerosis, but among children it was long-term epilepsy associated tumour. Long-term epilepsy associated tumours, hippocampal sclerosis and vascular malformations had the best post-operative outcomes. Malformations of cortical development and glial scars had the worst outcomes. Regarding differences between the two periods, the absolute number of operated patients increased (119 versus 140), and the age at surgery was higher in the second period (p = 0.04). The number of malformations of cortical development increased (p = 0.01), but the number of other tumours (p = 0.01) and specimens with no lesion (p = 0.03) decreased in the same period. CONCLUSION: This study is in line with contemporaneous research, reinforcing the previous knowledge on the underlying structural aetiologies, clinical practice, and surgical outcomes over more than two decades of experience. Our data provide realistic expectations about epilepsy surgery and highlight the need for further improvements in diagnosis and treatment paradigm for people with chronic epilepsy.

Introdução: Nas últimas décadas, a cirurgia ressectiva demonstrou ser uma opção valiosa no tratamento da epilepsia farmacorresistente. A classificação histopatológica foi de grande importância na orientação do doente. Os objetivos deste estudo foram caracterizar a nossa série de cirurgia de epilepsia ressectiva incluindo os diagnósticos histopatológicos, e compreender as diferenças na prática clínica entre dois períodos diferentes do programa de cirurgia da epilepsia. Material e Métodos: Realizou-se um estudo de coorte retrospetivo, incluindo doentes com epilepsia farmacorresistente submetidos a cirurgia ressectiva entre 1997 e 2021 no Centro Hospitalar e Universitário de Coimbra. Os diagnósticos histopatológicos foram classificados em sete categorias. Para análise comparativa, a coorte foi dividida em dois períodos consecutivos de 12 anos. Resultados: Um total de 259 doentes foram incluídos, sendo 228 (88%) adultos aquando da cirurgia. A mediana da duração da doença antes da cirurgia foi de 14 (amplitude interquartil 23) anos. Cinquenta e cinco (21%) doentes realizaram investigação invasiva pré-cirúrgica. O lobo temporal foi a região mais frequentemente operada (73%). Complicações pós-cirúrgicas major e minor foram identificadas em 21 (8%) doentes. Uma redução no número de antiepiléticos foi observada em 96 (37%) doentes após a cirurgia. O diagnóstico histopatológico mais comum foi a esclerose do hipocampo, mas nas crianças foi o tumor associado a epilepsia de longa duração. Tumores associados a epilepsia de longa duração, esclerose do hipocampo e malformações vasculares tiveram os melhores resultados pós-operatórios. Malformações do desenvolvimento cortical e cicatrizes gliais tiveram os piores resultados. Relativamente às diferenças entre os dois períodos, o número absoluto de doentes operados aumentou (119 versus 140), e a idade aquando da cirurgia foi maior no segundo período (p = 0,04). O número de malformações do desenvolvimento cortical aumentou (p = 0,01), mas o número de outros tumores (p = 0,01) e amostras sem lesão (p = 0,03) diminuiu no mesmo período. Conclusão: Este estudo está de acordo com a literatura atual, reforçando o conhecimento prévio sobre as etiologias estruturais, prática clínica e resultados cirúrgicos ao longo de mais de duas décadas de experiência. Os dados analisados fornecem expectativas realistas sobre a cirurgia de epilepsia e destacam a necessidade de melhorias no paradigma de diagnóstico e tratamento destes doentes.

Neutrophil/lymphocyte and monocyte/lymphocyte indexes as potential predictors of relapse at 1 year after diagnosis of pediatric multiple sclerosis: a single-center, exploratory and proof-of-concept study.

Introduction: Early identification of patients with a more unfavorable outcome in Multiple Sclerosis (MS) is crucial to optimize individualized treatment. Neutrophil-lymphocyte index (NLI) and monocyte-lymphocyte index (MLI) have been considered as potential biomarkers for disease prognosis. Our study aims to investigate the usefulness of NLI and MLI as predictors of relapse, disability progression, and lesion accumulation on magnetic resonance imaging (MRI) 1 year after diagnosis and treatment initiation, in pediatric-onset MS. Methods: A retrospective single-center study was conducted, including patients with diagnosis of MS established in pediatric age (<18 years old), at least 1-year of follow-up, and a complete blood count (CBC) performed at diagnosis. We collected the nearest-to-diagnosis NLI and MLI, as well as clinical and imaging variables, at diagnosis and 12 months later. Our cohort was further dichotomized into two groups, based on the presence of relapses. Statistical significance was considered for p < 0.05. Results: Eighteen patients (n = 18) were included. The relapsing group had higher mean, minimum, and maximum values for both NLI (5.17 ± 5.85, range: 1.57-11.92) and MLI (0.35 ± 0.22, range: 0.19-0.59), compared to the non-relapsing group (2.19 ± 1.63, range: 1.12-7.32 for NLI, and 0.24 ± 0.09, range: 0.14-0.44 for MLI). A higher percentage of patients in the relapsing group had increased NLI (>1.89, 66.7%) and MLI (>0.21, 66.7%) values than those in the non-relapsing group (46.7%). Patients who presented new T2-hyperintense lesions on MRI after 1 year of follow-up also had higher mean, minimum, and maximum values of both biomarkers. Patients who did not achieve No Evidence of Disease Activity-3 (NEDA-3) state exhibited higher values for both ratios. However, in our sample, no statistically significant correlations were found between MLI and NLI values and the clinical and imaging variables considered. Conclusion: The ease of obtaining NLI and MLI from routine blood tests renders them useful biomarkers as a screening tool in longitudinal follow-up. Our study was based on a very small sample size, but it allowed us to verify the feasibility of the protocol used. It is intended to involve other centers in the next phase of this work, testing the possible usefulness of the indices under analysis on a larger sample.

Cytogenomic Analysis of Long-Term Epilepsy-Associated Tumors Using an Array-Based CGH Strategy.

A palette of copy number changes in long-term epilepsy-associated tumors (LEATs) have been reported, but the data are heterogeneous. To better understand the molecular basis underlying the development of LEATs, we performed array-comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in 8 cases of LEATs. A high number of aberrations were found in 4 patients, among which deletions predominated. Both whole-chromosome and regional abnormalities were observed, including monosomy 19, deletion of 1p, deletions of 4p, 12p, and 22q, and gain of 20p. The common altered regions are located mainly on chromosomes 19 and 4p, identifying genes potentially involved in biological processes and cellular mechanisms related to tumorigenesis. Our study highlights new genomic alterations and reinforces others previously reported, offering new molecular insights that may help in diagnosis and therapeutic decision-making.

Pediatric cerebral sinus venous thrombosis: clinical characterization of a Portuguese cohort.

INTRODUCTION: Pediatric cerebral sinus venous thrombosis (CSVT) is a rare entity. Risk factors differ from the adults, and treatment is not consensual. With this work, we aimed to characterize a pediatric cohort from two Portuguese tertiary centers. METHODS: All patients under 18 years old with confirmed CSVT admitted between 2006 and 2019 were retrospectively included. Demographics, clinical presentation, workup, and follow-up were evaluated. RESULTS: Fifty-three patients were included, 29 were male (54.7%). Median age was 5 years (IQR 11.08, range 0-17 years old). Headache, seizures and impairment of consciousness were the most frequent manifestations. A risk factor was identified in 90.6% (n = 48), mostly infections (43.8%; n = 21). CNS complications were comprised of hemorrhage, venous infarction, hydrocephalus and edema. Treatment included anticoagulation in 36 patients (67.9%), and there were no recurrences on follow-up. Prognosis was favorable, with most patients presenting no or only slight disability comparing to same age and sex children, on the follow-up. DISCUSSION: In this cohort, impairment of consciousness was the most frequent clinical presentation and infections were the most frequent risk factors. The outcome was mainly favorable, with most patients presenting none or mild disability and without recurrences on follow-up. Studies are needed to define the criteria for anticoagulation and its recommended duration in children.

DEPDC5 variant in focal cortical dysplasia: a case report and review of the literature.

Germline and 2-hit brain somatic variants in DEPDC5 gene, a negative regulator of the mammalian target of rapamycin (mTOR) pathway, are increasingly recognized in patients with focal cortical dysplasia (FCD). Next-generation targeted sequencing identified a heterozygous germline variant in DEPDC5 gene (c.3241A>C, p.Thr1081Pro), classified as of unknown significance, in a patient with clinical features compatible with DEPDC5 phenotype (FCD, focal epilepsy, attention-deficit/hyperactivity disorder and borderline intellectual functioning). This missense variant has previously been reported in two other epileptic patients. Although interpretation of missense variants remains a challenge, DEPDC5 variants in patients with FCD and epilepsy cannot be neglected. Null variants were the most frequently reported in FCD patients, but missense variants have been described as well. The recognition of DEPDC5 phenotype and the appropriate interpretation of the detected variants are essential, since it may have important treatment implications in the near future, namely the use of mTOR inhibitors.

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.

Ketogenic Diet for Refractory Childhood Epilepsy: Beyond Seizures Control, the Experience of a Portuguese Pediatric Centre.

INTRODUCTION: Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects. MATERIAL AND METHODS: Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital. RESULTS: In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/- 5.6). Of those, 18 had a ≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21). DISCUSSION: Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior. CONCLUSION: Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet.

Introdução: A dieta cetogénica é uma dieta com baixo teor de hidratos de carbono, que pode ser usada no tratamento da epilepsia infantil refratária. O principal objetivo deste estudo foi avaliar a eficácia nos doentes que completaram pelo menos três meses de dieta, no que respeita ao controlo das crises, comportamento e estado de alerta. Foi também avaliada a variação do número de fármacos antiepiléticos, as razões de descontinuação e os efeitos secundários. Material e Métodos: Análise retrospetiva dos processos clínicos dos doentes com epilepsia refratária sob dieta cetogénica, de outubro de 2007 a janeiro de 2018, num hospital pediátrico de nível 3. Resultados: Nos 29 doentes elegíveis, a média da idade de implementação foi 7,9 anos (+/­ 5,6). Destes, 18 tiveram uma redução ≥ 50% das crises, 19 tiveram uma melhoria marcada do comportamento e 18 do seu estado de alerta. Dos 15 que completaram 18 meses, a mediana do número de fármacos antiepiléticos permaneceu idêntica à do início (três fármacos). A principal razão de descontinuação foi por decisão familiar. Os principais efeitos secundários foram a hipercolesterolémia (n = 23) e a hipertrigliceridémia (n = 21). Discussão: Os resultados foram semelhantes aos obtidos noutras coortes, nomeadamente no que respeita à idade de início, à percentagem de doentes que completou a dieta, às razões da suspensão e à melhoria do comportamento e estado de alerta. Conclusão: Para além do controlo das crises, os doentes tiveram uma marcada melhoria do seu comportamento e estado de alerta. É necessário desenvolver estratégias para aumentar a adesão das famílias à dieta.

Recent Advances and Challenges of mTOR Inhibitors Use in the Treatment of Patients with Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of benign, noninvasive, and tumor-like lesions called hamartomas that can affect multiple organ systems and are responsible for the clinical features of the disease. In the majority of cases, TSC results from mutations in the TSC1 and TSC2 genes, leading to the overactivation of the mammalian target of rapamycin (mTOR) signalling pathway, which controls several cell functions, including cell growth, proliferation, and survival. The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. However, the intrinsic characteristics of these drugs and their systemic effects in such a heterogeneous condition pose many challenges in clinical practice, so that some questions remain unanswered. This article provides an overview of the pharmacological aspects of mTOR inhibitors about the clinical trials leading to their approval in TSC-related conditions and exposes current challenges and future directions associated with this promising therapeutic line.

Phenotyping GABA transaminase deficiency: a case description and literature review.

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.

A case of Epstein-Barr encephalitis with some curiosities.

We present the magnetic resonance imaging findings of an eight-year-old boy with Epstein-Barr virus (EBV) encephalitis, with special attention to lesion neuroanatomic distribution, diffusion-weighted images, and proton magnetic resonance spectroscopy (MRS). T2 and FLAIR-weighted images showed bilateral and symmetric basal nuclei lesions, with diffusion facilitation. MRS of the lesions demonstrated elevated lactate/lipid and excitatory neurotransmitters. The purpose of this report is to alert to this imagiologic pattern of EBV infection, and in particular to the fact that facilitated diffusion does occur on EBV encephalitis.

Memory functioning in children with epilepsy: frontal lobe epilepsy, childhood absence epilepsy, and benign epilepsy with centrotemporal spikes.

Specific cognitive deficits have been identified in children with epilepsy irrespective of results on intelligence tests. Memory deficits are traditionally attributed to temporal lobe epilepsy, whereas the impact of frontal lobe epilepsy on memory functions has remained controversial. The aim of this study was the examination of memory abilities in other childhood common epilepsy syndromes (frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE), and benign epilepsy with centrotemporal spikes (BECTS)) and the influence of epilepsy-related variables. Memory was examined in 90 children with epilepsy (each epilepsy group consisted of 30 children), aged 6-15, and compared with 30 control children. Children with FLE showed significant deficits in verbal and visual memory. In addition, type of epilepsy, earlier age at epilepsy onset, and longer active duration of epilepsy were associated with memory problems. Seizure frequency and treatment, however, did not influence memory performance. This study indicates that children with FLE show greater risk of developing memory deficits than children with CAE or BECTS, thus highlighting the importance of assessing also memory functions in frontal lobe epilepsy.

A 15-year follow-up of first unprovoked seizures: a prospective study of 200 children.

Epilepsy is associated with an extended spectrum of behaviour, psychiatric problems, and learning difficulties. The aim of this study was to establish the natural history of children with first unprovoked seizures. We studied prospectively 200 children under the age of 11 years who attended hospital emergency with a first unprovoked seizure. Demographic variables, personal and family history, neurological examination, EEG, psychiatric, and cognitive and educational profiles were analysed. Patients who developed epilepsy were characterised with respect to: time to relapse, remission rate, duration of epilepsy, neuroimaging, aetiology, epileptic syndrome, and therapeutic regimen. These results were compared to data of patients who had a single seizure over a follow-up period of 15 years. Thirty percent of children who had a first unprovoked seizure developed epilepsy. Partial seizure type was a statistically significant variable for the development of epilepsy. An EEG with epileptic abnormalities proved to be the main risk factor for recurrence. Fifteen years later, the group with epilepsy exhibited a 2.6 greater risk of psychiatric and academic comorbidities, compared to the group without epilepsy.

Pyridoxine-dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome.

We report 4 pyridoxine-dependent epilepsy patients in which good outcome was determined in three. The 4 patients were male and aged from 7 to 24 years old (from three unrelated Caucasian families). A clinical diagnosis of neonatal pyridoxine-dependent epilepsy was confirmed by biochemical and genetic studies. Clinical evaluation was performed and medical records were reviewed for therapy implementation and management, neurodevelopment outcome, magnetic resonance imaging, and electroencephalography. All were taking pyridoxine treatment and were seizure-free. Elevated urinary alpha-aminoadipic semialdehyde excretion was found in all patients. Antiquitin gene analysis identified a large homozygous deletion in one patient and two heterozygous mutations in the others. Treatment with pyridoxine should be attempted for all cases of infantile and childhood refractory epilepsy, as has been the case over the last 20 years. Currently, urinary alpha-aminoadipic semialdehyde is a reliable biomarker of pyridoxine-dependent epilepsy, even under pyridoxine treatment. Detection of mutations in the antiquitin gene, encoding alpha-aminoadipic semialdehyde dehydrogenase, establishes the diagnosis and allows for adequate genetic counselling.

Intellectual functioning in children with epilepsy: frontal lobe epilepsy, childhood absence epilepsy and benign epilepsy with centro-temporal spikes.

PURPOSE: The purpose of our study is to describe intellectual functioning in three common childhood epilepsy syndromes - frontal lobe epilepsy (FLE), childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS). And also to determine the influence of epilepsy related variables, type of epilepsy, age at epilepsy onset, duration and frequency of epilepsy, and treatment on the scores. METHODS: Intellectual functioning was examined in a group of 90 children with epilepsy (30 FLE, 30 CAE, 30 BECTS), aged 6-15 years, and compared with a control group (30). All subjects obtained a Full Scale IQ ≥ 70 and they were receiving no more than two antiepileptic medications. Participants completed the Wechsler Intelligence Scale for Children - Third Edition. The impact of epilepsy related variables (type of epilepsy, age at epilepsy onset, duration of epilepsy, seizure frequency and anti-epileptic drugs) on intellectual functioning was examined. RESULTS: Children with FLE scored significantly worse than controls on WISC-III Verbal IQ, Full Scale IQ and Processing Speed Index. There was a trend for children with FLE to have lower intelligence scores than CAE and BECTS groups. Linear regression analysis showed no effect for age at onset, frequency of seizures and treatment. Type of epilepsy and duration of epilepsy were the best indicators of intellectual functioning. CONCLUSION: It is crucial that children with FLE and those with a longer active duration of epilepsy are closely monitored to allow the early identification and evaluation of cognitive problems, in order to establish adequate and timely school intervention plans.

Nonketotic hyperglycinemia: a cause of encephalopathy in children.

Nonketotic hyperglycinemia is a rare metabolic disorder with severe, frequently fatal, neurologic manifestations. Reliable and accurate diagnosis depends on careful interpretation of laboratory findings. The clinical suspicion should lead to determination of glycine in plasma and cerebrospinal fluid. Amino acid analysis presents diagnostic values for classic nonketotic hyperglycinemia, but it also should be performed in suspected cases of atypical nonketotic hyperglycinemia and in children with seizures, failure to thrive, behavior problems, and uncoordinated movements. Clinical assessment should be reinforced by demonstration of elevated cerebrospinal fluid-to-plasma glycine ratio. Confirmatory diagnosis requires enzymatic and genetic investigation of glycine cleavage system. An early diagnosis, though not affecting clinical outcome, allows proper genetic counseling, with the possibility of prenatal diagnosis. We report 3 cases of nonketotic hyperglycinemia, 2 typical neonatal and 1 atypical, diagnosed in Pediatric Hospital of Coimbra, Portugal, and investigated at Laboratory of Biochemical Genetics in 2004 to 2010 (incidence 1:47 455; prevalence 1:782 951).

[Neuropsychological evaluation in children with epilepsy: attention and executive functions in temporal lobe epilepsy]. / Evaluación neuropsicológica en niños con epilepsia: atención y funciones ejecutivas en epilepsia del lóbulo temporal.

INTRODUCTION: Attention and executive functions correspond to important areas of cognitive functioning associated with the frontal cortex. The study of attention and executive functions in children with epilepsy has focused on characterizing the group with frontal lobe epilepsy. Still, recent studies have identified deficits in these areas also in children with temporal lobe epilepsy (TLE). AIM: To investigate attention and executive functions in a group of children with TLE, also considering the influence of clinical variables (age at onset of epilepsy and evolution of seizures). SUBJECTS AND METHODS: Attention and executive functions were studied in a group of 24 children with TLE, aged 7-15 years and compared with 24 control children of the same age and socio-cultural level. Subjects were assigned the following tasks: Cancellation Task, Trail Making Test, Tower of London and Phonemic Verbal Fluency. RESULTS: The group with TLE performed significantly lower on selective, sustained and divided attention and on phonemic verbal fluency. In markers concerning commissions and omissions there were no differences between groups in any of the performed tests. A significant slowing of processing speed was reported. In addition, patients with earlier age at onset of epilepsy had more difficulties in sustained attention and planning abilities. CONCLUSION: These results sustain the need for evaluating and monitoring the area of attention, executive functions and processing speed in children and adolescents with temporal lobe epilepsy, above all those with earlier age at onset of epilepsy.

Atypical presentation of Leber's hereditary optic neuropathy associated to mtDNA 11778G>A point mutation--A case report.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder characterized by bilateral loss of central vision, most frequently found in young adult males. In most patients there are no other neurological manifestations and cerebral neuroimaging is normal, but some rare cases of "LHON plus" have been described. Classical LHON is mainly associated to mitochondrial DNA (mtDNA) mutations 11778G>A, 3460G>A and 14484T>C, localized in the coding regions for ND4, ND1 and ND6 of the complex I subunits of mitochondrial respiratory chain (MRC), respectively. We report a 12-year-old girl who presented with reduced visual acuity secondary to optic atrophy at 8 months of age, which led to a clinical diagnosis of LHON. Psychomotor regression, refractory epilepsy and progressive neurological abnormalities developed subsequently. Skeletal muscle histology and biochemical MRC function were normal (evaluated by dual wavelength spectrophotometry). A 11778G>A mtDNA point mutation (investigated by standard PCR and automatic sequencing methods) was identified in lymphocytes isolated from peripheral blood, muscle biopsy and cultured skin fibroblasts. The mother and other maternal relatives are carriers for the same mutation. This case is unusual for age of onset, gender, associated neurological findings and evolution.