Cortical mapping of receptive language processing in children using navigated transcranial magnetic stimulation.

We used a stepwise process to develop a new paradigm for preoperative cortical mapping of receptive language in children, using temporary functional blocking with transcranial magnetic stimulation (TMS). The method combines short sentences with a lexical decision task in which children are asked to point at a picture that fits a short sentence delivered aurally. This was first tested with 24 healthy children aged 4-16 years. Next, 75 sentences and 25 slides were presented to five healthy children in a clinical setting without TMS. Responses were registered on a separate computer, and facial expressions and hand movements were filmed for later offline review. Technical adjustments were made to combine these elements with the existing TMS equipment. The audio-recorded sentences were presented before the visual stimuli. Sentence lists were constructed to avoid similar stimuli in a row. Two different baseline lists were used before the TMS registration; the second baseline resulted in faster responses and was chosen as the reference for possible response delays induced by TMS. Protocols for offline reviews were constructed. No response, incorrect response, self-correction, delayed response, and perseveration were considered clear stimulation effects, while poor attention, discomfort, and other events were regarded as unclear. Finally, three children (6:2, 14:0, 14:10 years) with epilepsy and expected to undergo neurosurgery were assessed using TMS (left hemisphere in one; both hemispheres in the other two). In the two assessed bilaterally, TMS effects indicated bilateral language processing. Delayed response was the most common error. This is a first attempt to develop a new TMS paradigm for receptive language mapping, and further evaluation is suggested.

Parent reported health related quality of life (HRQoL) and behaviour in young people with epilepsy before and two years after epilepsy surgery.

PURPOSE: The aim of this study was to compare parent-reported Health Related Quality of Life (HRQoL) and behaviour of young people before (baseline) and two years after paediatric epilepsy surgery (follow-up). METHODS: The parents of 107 children who underwent epilepsy surgery completed surveys focussing on different aspects of child HRQoL and behaviour at baseline and follow-up. Parents of children with multiple disabilities (n = 27) completed five additional questions focussing on child HRQoL. Changes in scores between baseline and follow-up were compared using Wilcoxon signed-rank tests. Factors associated with changes in scores were analyzed using linear regression. RESULTS: HRQoL and behaviour were significantly improved at follow-up (p < 0.001). HRQoL was also significantly improved for children with multiple disabilities (p = 0.003). Factors independently associated with improvement in HRQoL on multivariable analysis were lower baseline scores (p < 0.001), seizure-free status (p < 0.001) and improvement in behaviour (p = 0.022). Factors independently associated with improvement in behaviour were higher baseline difficulties (p < 0.001), reduction in antiepileptic drug (AED) usage, (p < 0.001), seizure-free status (p = 0.04), younger age (p = 0.03), and improvements in HRQoL (p = 0.028). CONCLUSION: Parent rated HRQoL and behaviour had improved two years after epilepsy surgery. Seizure freedom was associated with both improvements in HRQoL and behaviour. Additionally, a reduction in AED usage contributed to reduced behavioural difficulties. All children undergoing epilepsy surgery should undergo assessment of HRQoL and behaviour at baseline and follow-up.

Parent-reported symptoms of ADHD in young people with epilepsy before and two years after epilepsy surgery.

The aim was to compare parent-reported symptoms of attention-deficit/hyperactivity disorder (ADHD) before (baseline) and two years after pediatric epilepsy surgery (follow-up). The parents of 107 children who underwent epilepsy surgery completed surveys including the Conners 10-item scale at baseline and follow-up. Changes in scores between baseline and follow-up were compared using paired sample t-test. Factors associated with changes in scores were analyzed using linear regression. Features of ADHD were significantly reduced at follow-up (p < 0.001). Items with the greatest reduction were items focusing on core aspects of the diagnostic criteria for ADHD. Fewer children were in the at-risk range for ADHD on the Conners 10-item scale at follow-up but this did not reach statistical significance (49% vs. 43%; p = 0.481). Factors independently significantly associated with improvement in ADHD symptoms on multivariable analysis were higher baseline scores (p < 0.001), seizure-free status (p = 0.029), and right-sided surgery (p = 0.031). Children who undergo epilepsy surgery have a high rate of ADHD symptoms. Parent-rated symptoms of ADHD improved at 2-year follow-up after epilepsy surgery. All children undergoing epilepsy surgery should undergo assessment for ADHD at baseline and follow-up.

Navigated transcranial magnetic stimulation for preoperative cortical mapping of expressive language in children: Development of a method.

We adjusted an object-naming task with repetitive navigated transcranial magnetic stimulation (rnTMS) originally developed for preoperative cortical language mapping in adults in order for it to be used in children. Two series of pictures were chosen for children above and below 10 years of age, respectively. Firstly, the series of pictures and the preferred speed of presentation were assessed for their applicability in children of different ages and abilities. Secondly, these series were used with rnTMS preoperatively in five children with epilepsy. Naming errors induced by the stimulation comprised no response, delayed response, semantic error, phonological error, and self-correction. Language laterality was compared with the results of a dichotic listening test and with neuropsychological tests with respect to general laterality, and general language abilities were considered with respect to the results of stimulation. One participant had below normal general language abilities, two had below-normal rapid naming, and three had slow and indistinct articulation. Laterality was only clear in two of the participants. All children required breaks of various durations during the process, and individual adjustments of the interpicture interval and other stimulation parameters were also made. We conclude that, after adjustment, rnTMS combined with an object-naming task can be useful for preoperative language mapping in children.

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes.

OBJECTIVES: Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. METHODS: Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed. RESULTS: Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe-except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients. CONCLUSION: Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

Intelligence two years after epilepsy surgery in children.

Intelligence before and two years after epilepsy surgery was assessed in 94 children and adolescents and related to preoperative IQ and seizure outcome. The median full-scale IQ was 70 before and two years after surgery. The proportion with a higher or unchanged postoperative IQ was 24 of 49 (49%) of those with an IQ of 70 and more before surgery, nine of 17 (53%) of those with an IQ of 50-69, and ten of 28 (36%) of those with an IQ of less than 50. A significant difference was found between the 47 individuals who became seizure-free and the 47 with persisting seizures, as 60% of the seizure-free children had a higher or unchanged IQ compared with 32% of the 47 who were not seizure-free. The cognitive outcome of children with intellectual disabilities was as good as that of children with average IQ. Thus, they should not be excluded from epilepsy surgery on the basis of low intellectual level.

Epilepsy surgery in children with accompanying impairments.

The aim of this study was to assess seizure outcome 2 years after epilepsy surgery in a consecutive series of paediatric patients, with special focus on children with learning disabilities and other neuroimpairments in addition to the epilepsy. Outcome 2 years after surgery was assessed in 110 of 125 children operated upon for drug resistant epilepsy in Gothenburg 1987-2006. More than half of the children had learning disabilities, 43% motor impairments and 30% a neuropsychiatric diagnosis. Fifty-six per cent of those with an IQ < 70 became seizure-free or had a >75% reduction in seizure frequency, and two thirds if the operation was a resection. The corresponding figure in those with more than 100 seizures per month was 15 out of 31, and another seven had a 50-75% reduction in seizure frequency. The message is that learning disability, motor impairment and psychiatric morbidity should not be contraindications for paediatric epilepsy surgery. More than half of the children with learning disabilities had a worthwhile seizure outcome, with even better results after resective surgery. Children with drug resistant epilepsy and additional severe neurological impairments should have the benefit of referral to a tertiary centre for evaluation for epilepsy surgery.

Cognitive development from two to ten years after pediatric epilepsy surgery.

The development of cognitive functions and the sustainability of seizure control between two and ten years after epilepsy surgery were prospectively investigated in 17 children and adolescents. Intelligence quotient remained stable. Learning capacity improved. Verbal memory improved in half of the subjects and declined in half, whereas figurative memory declined in most patients. Working memory improved as did attention regarding sustained attention and impulse control. In contrast, reaction times were longer, and the auditory attention span was shorter. Executive functions were not affected. Six subjects (35%) were seizure free at the 10-year follow-up, and a seizure reduction of more than 75% had been achieved in 13 (76%). Seizure control improved in five and seizures recurred in two subjects between the two- and the 10-year follow-up.

Speech, language, and cognitive dysfunction in children with focal epileptiform activity: A follow-up study.

We reviewed the medical history, EEG recordings, and developmental milestones of 19 children with speech and language dysfunction and focal epileptiform activity. Speech, language, and neuropsychological assessments and EEG recordings were performed at follow-up, and prognostic indicators were analyzed. Three patterns of language development were observed: late start and slow development, late start and deterioration/regression, and normal start and later regression/deterioration. No differences in test results among these groups were seen, indicating a spectrum of related conditions including Landau-Kleffner syndrome and epileptic language disorder. More than half of the participants had speech and language dysfunction at follow-up. IQ levels, working memory, and processing speed were also affected. Dysfunction of auditory perception in noise was found in more than half of the participants, and dysfunction of auditory attention in all. Dysfunction of communication, oral motor ability, and stuttering were noted in a few. Family history of seizures and abundant epileptiform activity indicated a worse prognosis.

Psychopathology, psychosocial functioning, and IQ before and after epilepsy surgery in children with drug-resistant epilepsy.

This is a prospective study of a consecutive series of children undergoing epilepsy surgery. The main aims were to evaluate the heterogeneity with respect to psychopathology and IQ, and to use a global assessment scale (Children's Global Assessment Scale [CGAS]) to evaluate psychosocial functioning. Clinical neuropsychiatric and neuropsychological assessments were made at baseline and at the 2-year follow-up in 24 patients, and changes were analyzed at an individual level. Psychiatric disorders (mainly attention deficit hyperactivity disorder and/or autism spectrum disorders) were found in 17 of 24 at some point. All except one child with psychiatric diagnoses before surgery still had at least one diagnosis at follow-up. Intellectual ability remained stable in the majority of cases, both in individuals with and in individuals without mental retardation. The CGAS illustrated the consequences of the extensive comorbidity in this cohort. The behavioral problems had been undiagnosed despite parental concern in many cases, indicating an unrecognized need for services for children with drug-resistant epilepsy.

Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: a prospective 2-year follow-up study.

Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure frequency in some children with drug-resistant epilepsy who are not suitable candidates for epilepsy surgery. It has been suggested that there may be positive cognitive and/or behavioral effects independent of seizure control. We describe the effects of VNS with respect to seizure frequency, cognition, and autistic symptoms and behavior in eight children and adolescents with medically intractable epilepsy and autism. In comparison to baseline, seizure frequency had not decreased in anyone in our series at the 2-year follow-up. In three cases, minor improvements in general functioning were noted, but there were no positive cognitive effects. This open prospective pilot study highlights the need for more prospective studies to prevent false expectations of improvement in this severely disabled group.

Comorbidity in severe developmental language disorders: neuropediatric and psychological considerations.

AIM: To explore possible patterns of comorbidity in children with severe developmental language disorders (DLD). METHODS: A retrospective investigation of the clinical records of 28 children relating to oral motor and language problems, psychological profiles, medical history and EEG findings. RESULTS: 36% of all the children had pure expressive language problems, 64% had combined expressive-receptive language problems and 57% had additional oral motor problems. Girls predominated in expressive-receptive problems, while boys predominated in oral motor problems. Children with expressive-receptive disorders were over-represented at the lower end of normal full-scale IQ (p = 0.015). Lower verbal than non-verbal IQ levels were almost as common as equal levels, but a lower non-verbal IQ than verbal IQ was also found. Pre/perinatal problems were found in 21%, and heredity for developmental language problems or dyslexia in 39%. There was a higher proportion of attention and motor problems, EEG abnormalities, and epileptic syndromes than in the general population (p < 0.001). CONCLUSION: In severe DLD, both pure expressive and mixed expressive-receptive problems are found, and oral motor problems are common. Gender differences regarding symptoms are present. Receptive language ability is associated with the full-scale IQ level. A high proportion of EEG abnormalities and epilepsy is found. There is a complex pattern of comorbidity between speech-language symptoms, psychological characteristics, heredity and EEG findings.

Language asymmetry and auditory attention in young adulthood after being born small-for-gestational age or with cardio-pulmonary resuscitation at birth.

A dichotic listening test with consonant-vowel syllables was used to assess language asymmetry and shift of attention in 42 young adults who had been in need of cardio-pulmonary resuscitation at birth, with a mild or moderate clinical course during the neonatal period (n = 31), or were born small-for-gestational age (SGA; n = 11) and compared with healthy controls (n = 17). All the participants were followed up prospectively and displayed no neurological or developmental deficits at 18 months of age. All the groups had an expected right-ear advantage during a baseline condition with no instructions to shift attention. The SGA group and the moderate resuscitated group displayed clear signs of an attenuation of the right-ear advantage and they were also less able to modify the ear preference in forced-attention conditions, compared with the control group. The main finding was that the groups with the most severe pre- and perinatal complications were also most affected on the dichotic listening test at adult age.

Neuropsychological follow-up into young adulthood of term infants born small for gestational age.

BACKGROUND: The aim of the study was to investigate whether children born small for gestational age without other complications nor signs of neurological impairment or developmental delay before 18 months of age may display neuropsychological impairments later in life. MATERIAL/METHODS: Neuropsychological outcome, school achievement, and social adjustment in young adulthood (21-28 years of age) were investigated in a prospectively followed group of 17 children born small for gestational age (SGA) and compared with 30 controls born with appropriate weight. A questionnaire including items about highest education, present social situation, and self-estimation of health was conducted. A comprehensive neuropsychological assessment of the main aspects of cognitive function was performed in 12 young adults from the SGA group and compared with 18 subjects selected as normal controls. Intelligence, verbal functions, visuo-spatial and visuo-constructive functions, learning and memory of words and figures, attention, lateral preference, motor functions, and cognitive adaptive functions were investigated. RESULTS: The young adults born SGA displayed lower intelligence quotients, specifically reduced verbal comprehension and deficits in figurative learning and memory functions, compared with normal controls. No differences in educational achievement and social adjustment were found. Neither were any differences observed in maternal education levels. CONCLUSIONS: Infants born SGA display a reduced cognitive capacity at young adult age compared with controls. However, this lower capacity is not considered sufficiently severe to affect educational level or social adjustment.