Brita Fritsch

Modulation of motor performance and motor learning by transcranial direct current stimulation.

PURPOSE OF REVIEW Transcranial direct current stimulation (tDCS) has shown preliminary success in improving motor performance and motor learning in healthy individuals, and restitution of motor deficits in stroke patients. This brief review highlights some recent work. RECENT FINDINGS Within the past years, behavioural studies have confirmed and specified the timing and polarity specific effects of tDCS on motor skill learning and motor adaptation. There is strong evidence that timely co-application of (hand/arm) training and anodal tDCS to the contralateral M1 can improve motor learning. Improvements in motor function as measured by clinical scores have been described for combined tDCS and training in stroke patients. For this purpose, electrode montages have been modified with respect to interhemispheric imbalance after brain injury. Cathodal tDCS applied to the unlesioned M1 or bihemispheric M1 stimulation appears to be well tolerated and useful to induce improvements in motor function. Mechanistic studies in humans and animals are discussed with regard to physiological motor learning. SUMMARY tDCS is well tolerated, easy to use and capable of inducing lasting improvements in motor function. This method holds promise for the rehabilitation of motor disabilities, although acute studies in patients with brain injury are so far lacking.

Topiramate selectively decreases intracortical excitability in human motor cortex.

Summary:  Purpose: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium‐channel blocker, as γ‐aminobutyric acid type A (GABAA)‐receptor agonist and as non–N‐methyl‐D‐aspartate (NMDA)‐glutamate receptor antagonist.

[Lateralizing and localizing signs and symptoms of epileptic seizures: significance and application in clinical practice].

ZusammenfassungAbsicht des vorliegenden Artikels ist es, die Relevanz der lateralisierenden und lokalisierenden Anfallssymptome in Hinsicht auf die Diagnose und Differentialdiagnose epileptischer Anfälle darzustellen. Die lateralisierende Bedeutung von Anfallssymptomen lässt sich häufig unmittelbar aus der Kenntnis der funktionellen Anatomie des Gehirns herleiten. Auf die kontralaterale Hirnhemisphäre als Ursprungshemisphäre des Anfalls weisen fokale klonische oder tonische und versive Anfälle sowie eine iktale unilaterale Dystonie hin. Postiktales Nasereiben wird vornehmlich mit der zum Anfallsursprung ipsilateralen Hand durchgeführt genauso wie unilaterales Zwinkern mit einem Anfallsursprung auf der gleichen Seite korreliert. Während eine postiktale Dysphasie auf eine epileptogene Zone in der dominanten Hirnhemisphäre hinweist, treten iktale Sprache, Automatismen bei erhaltenem Bewusstsein und iktales Erbrechen überwiegend auf, wenn der Anfall von der nicht dominanten Hemisphäre generiert wurde.Die Kenntnis der häufigeren lateralisierenden und lokalisierenden Anfallssymptome stellt im klinischen Alltag bei der ambulanten und stationären Erstdiagnostik und natürlich auch im Rahmen des Video-EEG-Monitorings eine große Hilfe von erheblicher praktischer Relevanz dar.SummaryThis report reviews the lateralising and localising signs of epileptic seizures in respect to the differential diagnosis of epilepsy. The lateralising value of epileptic signs and symptoms can frequently be derived from the neuroanatomy. Focal clonic, focal tonic, and versive seizures as well as ictal unilateral dystonia are associated with a seizure onset zone in the contralateral hemisphere. Postictal nose wiping is performed with the hand ipsilateral to the epileptogenic zone. Similarly, unilateral blinking points to an ispilateral seizure onset. Automatisms with preserved consciousness, ictal speech, and vomiting correlate to an epileptogenic zone in the nondominant hemisphere, while postictal dysphasia is produced by seizures arising from the dominant hemisphere. Lateralising and localising signs and symptoms of epileptic seizures are of great help in the differential diagnosis of epilepsy from the first diagnosis of epileptic events to presurgical video-EEG monitoring.

Reflex Seizures in Patients with Malformations of Cortical Development and Refractory Epilepsy

Summary:  Purpose: Malformations of cortical development (MCDs) are usually highly epileptogenic, and their hyperexcitability could facilitate the occurrence of reflex seizures. We sought to characterize reflex seizures in patients with MCDs and refractory epilepsy.

Prolonged generalized dystonia after chronic cerebellar application of kainic acid

Dystonia has traditionally been considered as a basal ganglia disorder, but there is growing evidence that impaired function of the cerebellum may also play a crucial part in the pathogenesis of this disorder. We now demonstrate that chronic application of kainic acid into the cerebellar vermis of rats results in a prolonged and generalized dystonic motor phenotype and provide detailed characterization of this new animal model for dystonia. c-fos expression, as a marker of neuronal activation, was increased not only in the cerebellum itself, but also in the ventro-anterior thalamus, further supporting the assumption of a disturbed neuronal network underlying the pathogenesis of this disorder. Preproenkephalin expression in the striatum was reduced, but prodynorphin expression remained unaltered, suggesting secondary changes in the indirect, but not in the direct basal ganglia pathway in our model system. Hsp70 expression was specifically increased in the Purkinje cell layer and the red nucleus. This new rat model of dystonia may be useful not only for further studies investigating the role of the cerebellum in the pathogenesis of dystonia, but also to assess compounds for their beneficial effect on dystonia in a rodent model of prolonged, generalized dystonia.

Predictive value of electrocorticography in epilepsy patients with unilateral hippocampal sclerosis undergoing selective amygdalohippocampectomy

The purpose of this study was to evaluate the predictive value of intraoperative electro-corticography (ECoG) in patients with unilateral hippocampal sclerosis (HS) undergoing transsylvian selective amygdalohippocampectomy (sAHE). ECoG was recorded before and after resection in 22 patients with medication-resistant mesial temporal lobe epilepsy. The sAHE was performed, regardless of ECoG findings. ECoG findings recorded from the mesiobasal temporal lobe (MTL) and lateral temporal lobe (LTL) before and after the sAHE were correlated with seizure outcome 12 months later. Ten patients had right-sided and 12 left-sided HS. Average age was 37.1 years. Pre-resection spikes were restricted to the MTL in 11 patients and to the LTL in one. In three patients spikes were recorded from MTL and LTL and in seven no spikes were recorded before the resection. Fifteen patients (68%) remained completely seizure-free and 19 (86%) were in Engels class I post-operatively. Patients with pre-resection spikes restricted to the MTL (n=11) remained seizure-free more frequently (9/11, 82%) compared with other patients (6/11, 55%; P=0.36). Pre-resection ECoG may be helpful in the prediction of seizure outcome in patients undergoing sAHE for mesial temporal lobe epilepsy. A larger study including more than 100 patients is needed to determine the predictive value of ECoG in patients with mesial temporal lobe epilepsy.

Glia: A Neglected Player in Non-invasive Direct Current Brain Stimulation

Non-invasive electrical brain stimulation by application of direct current (DCS) promotes plasticity in neuronal networks in vitro and in in vivo. This effect has been mainly attributed to the direct modulation of neurons. Glia represents approximately 50% of cells in the brain. Glial cells are electrically active and participate in synaptic plasticity. Despite of that, effects of DCS on glial structures and on interaction with neurons are only sparsely investigated. In this perspectives article we review the current literature, present own dose response data and provide a framework for future research from two points of view: first, the direct effects of DCS on glia and second, the contribution of glia to DCS related neuronal plasticity.

Status epilepticus and seizures induced by iopamidol myelography

PURPOSE To report that iopamidol myelography can induce status epilepticus (SE) in patients carrying the diagnosis of symptomatic epilepsy and to estimate the incidence of seizures in patients undergoing iopamidol myelography. METHODS We retrospectively identified all patients with seizures/SE associated with 1350 iopamidol myelographies during the last 5 years at our institution. The impact of cervical versus lumbar myelography was analysed. RESULTS Induced by iopamidol myelography two non-epileptic patients suffered from first generalised tonic-clonic seizures and a 67-year-old women with symptomatic epilepsy after a remote ischemic stroke developed a generalised tonic-clonic seizure evolving into a dialeptic and right nystagmus SE (i.e. complex focal status) of 5-hour duration. The incidence of seizures in non-epileptic patients was 0.15%. The incidence of seizure induction for lumbar myelography was lower than for myelographies that included the cervical subarachnoid space. CONCLUSIONS Iopamidol myelography (especially if cervical) is associated with a risk of seizures in non-epileptic individuals and can induce SE in patients with epilepsy. Patients should be informed about the risk of seizure induction.

Anodal Transcranial Direct Current Stimulation Enhances Survival and Integration of Dopaminergic Cell Transplants in a Rat Parkinson Model

Abstract Restorative therapy concepts, such as cell based therapies aim to restitute impaired neurotransmission in neurodegenerative diseases. New strategies to enhance grafted cell survival and integration are still needed to improve functional recovery. Anodal direct current stimulation (DCS) promotes neuronal activity and secretion of the trophic factor BDNF in the motor cortex. Transcranial DCS applied to the motor cortex transiently improves motor symptoms in Parkinson’s disease (PD) patients. In this proof-of-concept study, we combine cell based therapy and noninvasive neuromodulation to assess whether neurotrophic support via transcranial DCS would enhance the restitution of striatal neurotransmission by fetal dopaminergic transplants in a rat Parkinson model. Transcranial DCS was applied daily for 20 min on 14 consecutive days following striatal transplantation of fetal ventral mesencephalic (fVM) cells derived from transgenic rat embryos ubiquitously expressing GFP. Anodal but not cathodal transcranial DCS significantly enhanced graft survival and dopaminergic reinnervation of the surrounding striatal tissue relative to sham stimulation. Behavioral recovery was more pronounced following anodal transcranial DCS, and behavioral effects correlated with the degree of striatal innervation. Our results suggest anodal transcranial DCS may help advance cell-based restorative therapies in neurodegenerative diseases. In particular, such an assistive approach may be beneficial for the already established cell transplantation therapy in PD.

Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.