Gerd Viggedal

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.

Speech, language, and cognition in preschool children with epilepsy

We studied expressive and receptive language, oral motor ability, attention, memory, and intelligence in 20 6‐year‐ old children with epilepsy (14 females, six males; mean age 6y 5mo, range 6y–6y 11mo) without learning disability, cerebral palsy (CP), and/or autism, and in 30 reference children without epilepsy (18 females, 12 males; mean age 6y 5mo, range 6y–6y 11mo). Ten children had partial, six primarily generalized, and four unclassified epilepsy. Fourteen were having monotherapy and six were taking two or more antiepileptic drugs; 13 children were free from seizures 3 months before the assessment. Results show no statistically significant difference between the groups concerning Verbal IQ, expressive and receptive grammar, and receptive vocabulary. The children with epilepsy had a significantly lower Performance IQ and lower scores in tests of oral motor ability, articulation, emerging literacy, auditory attention, short‐term memory, and rapid word retrieval. Parent ratings revealed no significant difference in communicative ability. Polytherapy and early onset of epilepsy influenced some results. Preschool children with epilepsy without learning disability, CP, and/or autism may have receptive verbal ability within the normal range but visuoperceptual, auditory attentional, and speech‐language difficulties that could affect school achievement. Careful testing of children with epilepsy who appear to be functioning within the normal range is needed because this may reveal specific impairments that require appropriate professional input.

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 (Childrens 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.

Follow-up into young adulthood after cardiopulmonary resuscitation in term and near-term newborn infants. I. Educational achievements and social adjustment.

Aim: Long‐term sequelae after perinatal asphyxia have generally been assessed at preschool or school age. The aim of the study was to confirm the hypothesis that there could be impairment of cognitive and memory functions that does not become apparent until education and adult life impose special demands. Methods: Seventy‐one term or near‐term newborns in need of cardiopulmonary resuscitation because of presumed perinatal asphyxia were investigated with evoked EEG potentials during the first week of life and were investigated at a follow‐up clinic until 18 mo of age. At that time 12 subjects showed signs of neuro‐developmental impairment. The remaining 59 were considered healthy. They were contacted at young adult age and given a questionnaire containing questions about type of education, need for extra support at school, present activity/employment, living conditions, spare‐time activities and self‐estimation of health. Results: Thirty‐five control subjects were approached at the same time. From the group that was resuscitated at birth, 53 questionnaires were returned and 30 from the control group. Although the resuscitated subjects had signs of both encephalopathy and pathologic evoked responses during their neonatal period, the questionnaire revealed that they had coped with school equally as well as their peers, that the rate of entering university studies was the same and that living conditions were similar between the groups.

Follow‐up into young adulthood after cardiopulmonary resuscitation in term and near‐term newborn infants. II. Neuropsychological consequences

Aim: Brain injury after neonatal cardiopulmonary resuscitation in the term baby is often described as an all‐or‐nothing phenomenon, but little is known about possible late cognitive consequences. The aim of this study was therefore to investigate whether children who needed cardiopulmonary resuscitation because of presumed mild and moderate intra‐partum asphyxia with no evidence of neurological impairments at 18 mo of age may display neuropsychological impairments later in life. Methods: A long‐term follow‐up of young adults was carried out. A blinded comprehensive neuropsychological assessment of the main aspects of cognitive functions was made. The subjects who were resuscitated were divided into two groups according to the clinical course: 20 cases with mild asphyxia and 11 cases with moderate asphyxia, all followed prospectively and compared with 18 healthy controls. The 31 subjects were born at term or near‐term and selected randomly from 59 infants born in 1969–1978 at Sahlgrens Hospital, Göteborg. All infants with early neurological impairments were excluded. Results: No major differences could be established between the two clinical groups and normal controls in any aspects of cognitive function or intelligence. All the groups performed within the normal range in all tests. A tendency toward minor deficits in verbal ability in the mild group compared to the controls was found. Only one subject had a clear, defined memory deficit.

Comorbidity in severe developmental language disorders: Neuropediatric and psychological considerations: Comorbidity in severe developmental language disorders

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).

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

ObjectivesOur 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.MethodsPediatric 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.ResultsNineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9xa0years. All patients alive at the time of data registration at a median age of 6xa0years. 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 3.3xa0mmol/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.ConclusionKetogenic 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.

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.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty‐six epilepsy centers and members of “E‐PILEPSY” (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co‐normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

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.