Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (four female, two male; plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition

Seizures and epilepsy in patients with ischaemic stroke

Background With the increased efficacy of stroke treatments, diagnosis and specific treatment needs of patients with post-stroke seizures (PSS) and post-stroke epilepsy have become increasingly important. PSS can complicate the diagnosis of a stroke and the treatment of stroke patients, and can worsen post-stroke morbidity. This narrative review considers current treatment guidelines, the specifics of antiseizure treatment in stroke patients as well as the state-of-the-art in clinical and imaging research of post-stroke epilepsy. Treatment of PSS needs to consider indications for antiseizure medication treatment as well as individual clinical and social factors. Furthermore, potential interactions between stroke and antiseizure treatments must be carefully considered. The relationship between acute recanalizing stroke therapy (intravenous thrombolysis and mechanical thrombectomy) and the emergence of PSS is currently the subject of an intensive discussion. In the subacute and chronic post-stroke phases, important specific interactions between necessary antiseizure and stroke treatments (anticoagulation, cardiac medication) need to be considered. Among all forms of prevention, primary prevention is currently the most intensively researched. This includes specifically the repurposing of drugs that were not originally developed for antiseizure properties, such as statins. PSS are presently the subject of extensive basic clinical research. Of specific interest are the role of post-stroke excitotoxicity and blood–brain barrier disruption for the emergence of PSS in the acute symptomatic as well as late (> 1 week after the stroke) periods. Current magnetic resonance imaging research focussing on glutamate excitotoxicity as well as diffusion-based estimation of blood–brain barrier integrity aim to elucidate the pathophysiology of seizures after stroke and the principles of epileptogenesis in structural epilepsy in general. These approaches may also reveal new imaging-based biomarkers for prediction of PSS and post-stroke epilepsy. Conclusion PSS require the performance of individual risk assessments, accounting for the potential effectiveness and side effects of antiseizure therapy. The use of intravenous thrombolysis and mechanical thrombectomy is not associated with an increased risk of PSS. Advances in stroke imaging may reveal biomarkers for PSS

Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS

an experimental animal study

Das wechselseitige Verhältnis zwischen anhaltender epileptischer Aktivität während des Status epilepticus (SE) und der Körpertemperatur bzw. ihrer Regulation ist komplex und in vielen Fragen ungeklärt. Ziel der vorliegenden Arbeit war zum einen, den Einfluss der externen Senkung der Körpertemperatur auf den SE, und zum anderen den Einfluss des motorischen und des limbischen (non-konvulsiven) SE auf die Thermoregulation zu untersuchen. Ein etabliertes in vivo Model des SE mit wachen, frei beweglichen Ratten wurde durch die Anlage einer epiduralen Temperatursonde ergänzt. So war es möglich, den Einfluss von Körpertemperaturveränderungen simultan zu den epileptiformen Entladungen und den motorischen Anfallsmanifestationen des SE zu untersuchen. Bei den Tieren konnte umgekehrt der Einfluss unterschiedlicher semiologischer Manifestationen des SE (konvulsiv vs. non-konvulsiv) auf die Körpertemperatur systematisch beobachtet werden. Durch externe Hypothermie wurde die Körpertemperatur der Tiere herabgesetzt. Dabei konnte ein antikonvulsiver Effekt auf die motorischen Anfälle nachgewiesen werden; dieser Effekt wurde durch die gleichzeitige Gabe von Diazepam in subtherapeutischen Dosen auf die elektrophysiologischen Parameter des SE erweitert. Umgekehrt zeigte sich, dass der generalisierte motorische SE mit einer anhaltenden Temperaturerhöhung einhergeht. Bei Tieren mit limbischem SE normalisierte sich eine initiale Temperaturerhöhung, allerdings verlief dieser Prozess sehr protrahiert. Um eine mögliche subtile Störung der Thermoregulation während des limbischen SE zu untersuchen, wurden Tiere in einem limbischen SE einer externen Hypothermie ausgesetzt. Mit diesem methodischen Ansatz ließ sich eine deutliche Störung der Thermoregulation im Vergleich zu naiven, ebenfalls der Kühlung ausgesetzten Tieren aufzeigen. Die Ergebnisse der verschiedenen Versuchsreihen werden bezüglich ihrer Implikationen für die Behandlung des SE und die Pathophysiologie der Thermoregulation während des SE kritisch diskutiert.The reciprocal relationship between the sustained epileptic activity during status epilepticus (SE) and the body temperature (or its regulation) is complex and remains in part elusive. The purpose of the present study was to investigate both the effect of external hypothermia on SE and the effect of motor and limbic (non-convulsive) SE on thermoregulation. An established in vivo model of SE with awake, freely moving rats was amended by implementing a temperature probe. By this means it became possible to investigate simultaneously the effect of body temperature changes on both epileptic activity and motor manifestations of the SE. Vice versa, the animals could systematically be monitored for the effect of the different semiological manifestations of SE (convulsive vs. non-convulsive) on the body temperature. The body temperature was decreased by application of external hypothermia; an anticonvulsive effect on motor seizure activity could be observed. Adding sub- therapeutic dosages of Diazepam resulted in additional suppression of electrographic parameters. On the other hand, it could be shown that generalised motor SE is associated with a long-lasting temperature elevation. In animals in limbic SE the initial temperature elevation normalised; however, this normalisation was considerably delayed. In order to investigate a subtle dysfunction of the thermoregulation during limbic SE, animals in limbic SE were exposed to external hypothermia. In comparison to naïve animals, also exposed to hypothermia, a noticeable disturbance of thermoregulation could be demonstrated with this methodical approach. The results of the various experimental series will be critically discussed in regard to implications for SE treatment and to the pathophysiology of thermoregulation during SE

100 Jahre Dieter Janz

Am 20.04.2020 jährt sich zum 100. Mal der Geburtstag von Dieter Janz. Ihm zu Ehren erscheint dieses Heft der Zeitschrift für Epileptologie mit dem Ziel, das Wirken von Dieter Janz der letzten fünf Jahrzehnte nachzuzeichnen und neue Erkenntnisse zu dem nach ihm benannten Janz-Syndrom (juvenile myoklonische Epilepsie) zusammenzufassen.The 20 April 2020 marks the centenary of Dieter Janz’s birth. This issue of Zeitschrift für Epileptologie is published in his honor with the aim of tracing the work of Dieter Janz over the last five decades and summarizing new findings on the Janz syndrome (Juvenile Myoclonic Epilepsy), which is named after him

Factors predicting 10-year seizure freedom after temporal lobe resection

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Resective surgery is an established and evidence-based treatment approach in pharmacoresistant temporal lobe epilepsy (TLE). Extra-long-term follow-up data are important to allow for good patient counseling. So far, only few trials provide prospective or retrospective data exceeding 5 years.</jats:p> </jats:sec><jats:sec> <jats:title>Objective</jats:title> <jats:p>This study aimed to present data of continuous seizure outcome over an extended time period, with a particular focus on patients who remained seizure free for 10 years.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We analyzed seizure outcome after epilepsy surgery for TLE in 46 consecutive patients, who were seen on an annual basis for 10 years in a single center (Epilepsy Center Berlin Brandenburg). Factors for remaining seizure free for 10 years were determined by univariate analysis.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The class I outcome changed each year by 74–78%. Of the patients, 63% remained continuously in Engel class I (48% Engel Class IA for 10 years) for 10 years. Six patients were never seizure free (12.5%). After 10 years, 35% of the patients were cured (i.e., seizure-free without medication). A higher number of antiepileptic drugs and seizures before surgery as well as the indication for invasive presurgical monitoring were associated with “unsuccessful surgery.”</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>With almost half of the patients completely seizure free and more than a third “cured,” epilepsy surgery remains the mainstay of therapy for TLE patients. Analysis in larger cohorts with extra-long-term follow-up is needed to assess good prognostic factors and other postsurgical outcome issues such as neuropsychological, psychiatric, and psychosocial outcomes.</jats:p> </jats:sec&gt

Impairments in path integration, rotational memory and balancing in patients with temporal lobe epilepsy

Objectives The vestibulo-medial temporal lobe (MTL) axis model proposes that the vestibular system and the MTL are tightly linked both structurally and functionally so that alterations of one structure should entail disturbances in the other. Accordingly, patients with temporal lobe epilepsy (TLE) with their functional and possible structural temporal lobe pathology should show deficits in vestibular-related behaviour. This study aimed at assessing behavioural deficits related to a suspected disturbance of the vestibulo-MTL axis in patients with TLE.Methods Twenty patients with TLE (46.7±15.1 years, seven females) and their age-matched and gender-matched controls (46.7±15.1, seven females) underwent three test batteries that challenged vestibular and MTL functions: balancing, path integration (triangle completion test) and rotational memory. In addition, participants underwent a structural MRI for grey matter analysis using voxel-based morphometry.Results Compared with controls, patients with TLE showed significantly inferior performance in all three behavioural tests, with large effect sizes. There were no significant grey matter differences between the two groups.Conclusion These results indicate a potential disturbance in the vestibulo-MTL axis in TLE; these are to be verified by future large-scale studies. In the current study, these behavioural deficits emerged without evidence of any brain volume differences between the patients and their controls as depicted by high-resolution MRI. This speaks for a dissociation between functional and structural alterations in TLE