Cortical excitability measured with transcranial magnetic stimulation in children with epilepsy before and after antiepileptic drugs.

AIM: To evaluate cortical excitability with transcranial magnetic stimulation (TMS) in children with new-onset epilepsy before and after antiepileptic drugs (AEDs). METHOD: Fifty-five drug-naïve patients (29 females, 26 males; 3-18y), with new-onset epilepsy were recruited from 1st May 2014 to 31st October 2017 at the Child Neurology Department, Queen Silvia's Children's Hospital, Gothenburg, Sweden. We performed TMS in 48 children (23 females, 25 males; mean [SD] age 10y [3y], range 4-15y) with epilepsy (27 generalized and 21 focal) before and after the introduction of AEDs. We used single- and paired-pulse TMS. We used single-pulse TMS to record resting motor thresholds (RMTs), stimulus-response curves, and cortical silent periods (CSPs). We used paired-pulse TMS to record intracortical inhibition and facilitation at short, long, and intermediate intervals. RESULTS: There were no differences in cortical excitability between children with generalized and focal epilepsy at baseline. After AED treatment, RMTs increased (p=0.001), especially in children receiving sodium valproate (p=0.005). CSPs decreased after sodium valproate was administered (p=0.050). As in previous studies, we noted a negative correlation between RMT and age in our study cohort. Paired-pulse TMS could not be performed in most children because high RMTs made suprathreshold stimulation impossible. INTERPRETATION: Cortical excitability as measured with RMT decreased after the introduction of AEDs. This was seen in children with both generalized and focal epilepsy who were treated with sodium valproate, although it was most prominent in children with generalized epilepsy. We suggest that TMS might be used as a prognostic tool to predict AED efficacy. WHAT THIS PAPER ADDS: Resting motor threshold (RMT) correlated negatively with age in children with epilepsy. No differences in cortical excitability were noted between patients with generalized and focal epilepsy. Treatment with antiepileptic drugs decreased cortical excitability as measured with transcranial magnetic stimulation (TMS). Decreased cortical excitability with increased RMT was recorded, especially after sodium valproate treatment. Paired-pulse TMS was difficult to perform because of high RMTs in children.

Medición de la excitabilidad cortical con estimulación magnética transcraneal en niños con epilepsia antes y después de los fármacos antiepilépticos OBJETIVO: Evaluar la excitabilidad cortical con estimulación magnética transcraneal (EMT) en niños con epilepsia de nueva aparición antes y después del uso de un fármaco antiepiléptico (FAE). MÉTODO: Cincuenta y cinco pacientes sin tratamiento previo (29 mujeres, 26 varones; de 3-18 años), con epilepsia de nueva aparición fueron reclutados del 1 de mayo de 2014 al 31 de octubre de 2017 en el Departamento de Neurología Infantil del Hospital de Niños Queen Silvia, en Gotemburgo, Suecia. Se realizó EMT en 48 niños (23 mujeres, 25 varones; media [DE] de 10 años [3 años], rango 4-15 años) con epilepsia (27 generalizada y 21 focal) antes y después de la introducción de los FAE. Usamos EMT de pulso único y de pulso emparejado. Utilizamos EMT de pulso único para registrar umbrales motores en reposo (UMR), curvas de estímulo-respuesta y períodos silenciosos corticales (PSC). Usamos EMT de pulso emparejado para registrar la inhibición y la facilitación intracorticales a intervalos cortos, largos e intermedios. RESULTADOS: No hubo diferencias en la excitabilidad cortical entre niños con epilepsia generalizada y focal al inicio. Después del tratamiento con FAE, los UMR aumentaron (p.0,001), especialmente en niños que recibieron valproato de sodio (p.0,005). Los PSC disminuyeron después de la administración del valproato sódico (p.0,050). Como en estudios anteriores, observamos una correlación negativa entre UMR y edad en nuestra cohorte de estudio. La EMT de pulso emparejado no se pudo realizar en la mayoría de los niños porque los UMR altos hacían imposible la estimulación supraumbral. INTERPRETACIÓN: La excitabilidad cortical medida con UMR disminuyó después de la introducción de los FAE. Esto se vio en niños con epilepsia generalizada y focal que fueron tratados con valproato de sodio, fue más prominente en niños con epilepsia generalizada. Sugerimos que EMT podría utilizarse como una herramienta de pronóstico para predecir la eficacia de la FAE.

Excitabilidade cortical medida com estimulação magnética transcraniana em crianças com epilepsia antes e após drogas antiepilépticas OBJETIVO: Avaliar a excitabilidade cortical com estimulação magnética transcraniana (TMS) em crianças com epilepsia de início recente antes e após drogas antiepilépticas (DAEs). MÉTODO: Cinquenta e cinco pacientes não expostos a drogas (29 do sexo feminino, 26 do sexo masculino; 3-18a), com epilepsia de início recente foram recrutadas de 1 de maio de 2014a a 31 de outubro de 2017 no Departamento de Neurologia Infantil, Hospital Rainha Silvia, Gothenburg, Suécia. Aplicamos TMS em 48 crianças (23 do sexo feminino, 25 do sexo masculino; média [DP] de idade 10a [3a], variação 4-15a) com epilepsia (27 generalizada e 21 focal) antes e após a introdução de DAEs. Usamos TMS de pulso único e pareado. O TMS de pulso único foi usado para registrar os limiares motores de repouso (LMR), curvas de estímulo-resposta, e períodos de silêncio cortical (PSC). Usamos TMS de pulsos pareados para registrar inibição e facilitação intracortical nos intervalos curto, longo e intermediário. RESULTADOS: Não houve diferenças na excitabiildade cortical entre crianças com epilepsia generalizada e focal na linha de base. Após o tratamento com DAE, o LMR aumentou (p=0,001), especialmente em crianças recebendo valproato de sódio (p=0,005). Os PSCs diminuíram após o valproato de sódio ser (p=0,050). Como em estudos prévios, notamos correlação negativa entre LMR e idade em nossa coorte. TMS de pulso pareado não pôde ser realizado na maioria das crianças porque os altos LMRs tornaram a estimulação supra-limiar impossível. INTERPRETAÇÃO: A excitabilidade cortical mensurada por LMR diminuiu após a introdução de DAEs. Isso foi visto em crianças com epilepsia generalizada e focal tratadas com valproato de sódio, embora tenha sido mais proeminente naquelas com epilepsia generalizada. Sugerimos que o TMS pode ser usada como ferramenta prognóstica para predizer a eficácia da DAE.

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.

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.

Microwave-based stroke diagnosis making global prehospital thrombolytic treatment possible.

Here, we present two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemorrhagic patients from healthy volunteers. The system was based on microwave scattering measurements with an antenna system worn on the head. Measurement data were analyzed with a machine-learning algorithm that is based on training using data from patients with a known condition. Computer tomography images were used as reference. The detection methodology was evaluated with the leave-one-out validation method combined with a Monte Carlo-based bootstrap step. The clinical motivation for this project is that ischemic stroke patients may receive acute thrombolytic treatment at hospitals, dramatically reducing or abolishing symptoms. A microwave system is suitable for prehospital use, and therefore has the potential to allow significantly earlier diagnosis and treatment than today.

Individual effects of varying stimulation intensity and response criteria on area of activation for different muscles in humans. A study using navigated transcranial magnetic stimulation.

BACKGROUND: When using transcranial magnetic stimulation, a stimulation intensity defined as a certain level above the threshold for activation of a hand muscle is commonly used, disregarding the fact that the areas of activation for different muscles may have varying response characteristics intra- and interindividually. OBJECTIVE: To study the response characteristics of different muscles and compare them within and between individuals. Also to investigate the effect of varying stimulation intensity (defined in two different ways) and amplitude criterion for response, on the sizes of the activation areas for different muscles. METHODS: A system of transcranial magnetic stimulation with navigation capacity where the stimulation intensity can be defined in terms of the electric field strength in the tissue was used. Four different muscles were investigated in healthy adults. The threshold for activation at rest (RMT) of the different muscles and their respective areas of activation were quantified using three different stimulus intensities (100, 110 and 120% RMT) and two criteria for response amplitude (20 and 50 µV). RESULTS: Responses could readily be determined using 20 µV as response limit. The RMTs for different muscles varied within and between individuals. The degree to which the area depended on stimulation intensity differed between muscles intra- and interindividually. All results were statistically significant (P < 0.05 or less). CONCLUSIONS: The response characteristics vary between muscles within an individual and between individuals for a certain muscle. Thus, for optimal accuracy when delineating the activation area, the investigation should be adapted to each particular muscle.