Chemogenetic therapy strongly suppresses hippocampal excitability and spontaneous seizures in a rat model for temporal lobe epilepsy

The hippocampus plays a crucial role in seizure generation in temporal lobe epilepsy (TLE), a common form of medication-resistant epilepsy. This preclinical study evaluated chemogenetics as a therapy for TLE. In this approach, excitatory neurons of the epileptic hippocampus were selectively inhibited through ligand-based activation of an inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD). The intraperitoneal kainic acid rat model for TLE was used. Animals were injected in right hippocampus with adeno-associated viral vector carrying CamKIIα-hM4Di-mCherry. Two weeks after injection, rats were implanted with electrodes. Dentate gyrus excitability was assessed by recording perforant path evoked potentials (EPs; n=8) before and after activating DREADDs with subclinical doses of clozapine (0.1 mg/kg, s.c.). Seizure suppression was determined using continuous video-EEG recordings (n=7) during a baseline period of seven days and three days of treatment with clozapine (0.1 mg/kg/24h, s.c.). Clozapine-induced activation of DREADDs suppressed synaptic transmission (field excitatory postsynaptic potential amplitude and slope reduced with 73%±12% and 65%±12% respectively) and postsynaptic neuronal activation (population spike surface area reduced with 53%±18) in dentate gyrus. In addition, in four of seven animals, DREADD activation led to complete suppression of spontaneous seizures for two to five hours. Activating hM4Di DREADDs in excitatory hippocampal neurons decreases excitability of dentate gyrus and temporary suppresses spontaneous seizures in a rat model for TLE. We believe that after optimization, this technique will lead to prolonged seizure freedom, making it a promising tool for clinical applications

Vestibular Infant Screening (VIS)–Flanders : results after 1.5 years of vestibular screening in hearing-impaired children

Due to the close anatomical relationship between the auditory and vestibular end organs, hearing-impaired children have a higher risk for vestibular dysfunction, which can affect their (motor) development. Unfortunately, vestibular dysfunction often goes unnoticed, as vestibular assessment in these children is not standard of care nowadays. To timely detect vestibular dysfunction, the Vestibular Infant Screening–Flanders (VIS–Flanders) project has implemented a basic vestibular screening test for hearing-impaired infants in Flanders (Belgium) with a participation rate of 86.7% during the first year and a half. The cervical Vestibular Evoked Myogenic Potentials (cVEMP) test was applied as vestibular screening tool to map the occurrence of vestibular (mainly saccular) dysfunction in this population. At the age of 6 months, 184 infants were screened. No refers on vestibular screening were observed in infants with permanent conductive hearing loss. In infants with permanent sensorineural hearing loss, a cVEMP refer rate of 9.5% was observed. Failure was significantly more common in infants with severe-profound compared to those with mild-moderate sensorineural hearing loss (risk ratio = 9.8). Since this is the first regional study with a large sample size and successful participation rate, the VIS–Flanders project aims to set an example for other regions worldwide

Der Hörsturz : neuere Erkenntnisse zur Therapie

Unter Hörsturz versteht man einen plötzlich, aus scheinbar vollem Wohlbefinden heraus auftretenden, einseitigen, seltener beidseitigen Hörverlust. Meistens bemerkt der Patient beim Aufwachen, daß er einseitig schlechter hört, in vielen Fällen in Kombination mit einem Ohrenrauschen, selten begleitet von Schwindelgefühlen. Aber nicht jeder akute Hörverlust ist ein Hörsturz. Nur eine plötzlich auftretende Störung im Bereich des Innenohres wird als Hörsturz bezeichnet

Acoustic Hearing Implants for Mixed Hearing Loss: A Systematic Review

A systematic review of literature to determine the clinical outcome and safety of the range of acoustic hearing implants (AHIs) in adults with mixed hearing loss (MHL).status: publishe

Acoustic hearing implants for mixed hearing loss: a systematic review

status: publishe