Abstracts

Rationale: Status epilepticus (SE) that is refractory to anti-epileptic drugs typically has a poor prognosis, but patients may recover well if seizures can be terminated. We have recently developed and published novel methods for using transcranial pulsed ultrasound (TPU) to stimulate brain activity (Tufail et al, 2010) . TPU can also synchronize intact hippocampal oscillations in high-frequency sharp-wave and gamma bands without producing damage. Since epileptic seizures have been attributed to runaway excitation in certain brain circuits including the hippocampus, we hypothesized TPU can provide an interference stimulus source capable of terminating aberrant activity observed during electrographic seizures. Thus, TPU may represent a brain stimulation method capable of providing rapid relief of SE during neurological emergencies.Methods: We studied the acute effects of transcranial US stimulation on healthy and kainic acid (KA) induced status epilepticus mice. We also studied the effect of US stimulation in freeze lesion models of polymicrogyria (cortical dysplasia). Efficacy of seizure control was measured by continuous fine wire EMG, intracranial extracellular recordings and monitoring duration of behavioral signs of seizure activity. Functional activity maps were constructed using antibodies against c-fos and compared before and after US stimulation of KA-induced status epilepticus mice.Results: Low-intensity continuous wave ultrasound (0.35 MHz) was applied for 2 to 10 seconds during SE. TPU significantly attenuated electromyographic seizures, as well as reduced the duration and severity of SE as indicated by Racine stage monitoring. Mice tolerated the TPU treatment procedures well. Conclusions: Our preliminary results suggest the feasibility of using ultrasonic neuromodulation for the acute treatment of status epilepticus. TPU holds the potential to be a viable noninvasive therapeutic paradigm for refractory status epilepticus. Reference: Transcranial pulsed ultrasound stimulates intact brain circuits. Tufail Y, Matyushov A, Baldwin N, Tauchmann ML, Georges J, Yoshihiro A, Tillery SI, Tyler WJ. Neuron. 2010 Jun 10;66(5):681-94