Stimulus Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs) and its Association with Non-convulsive Status Epilepticus in Critically Ill Patients.

Stimulus induced repetitive periodic or ictal discharges (SIRPIDs) are a commonly observed EEG pattern in critically ill patients. However, the epileptic significance of SIRPIDs remain unclear. We identified and reviewed 55 cases with SIRPIDs according to the ACNS criteria. SIRPIDs occurred after standardized painful stimuli during a standard 20-minute EEG. These cases were investigated regarding their relation to non-convulsive status epilepticus (NCSE) according to Salzburg Consensus Criteria and in-hospital mortality. In 37/55 patients (67.3%), SIRPIDs were associated with NCSE. In most patients (26/37 cases, 70.3%) with concurrent status epilepticus, SIRPIDs occurred after status epilepticus (on average 4.8 days later), but in 3/37 patients (8.1%) they were observed before a later status epilepticus. In four cases (4/37 cases, 10.8%), SIRPIDs appeared both before and after an episode of NCSE and in other four cases the two patterns coexisted in the same EEG. In 50% of the patients, status epilepticus was refractory, super-refractory or the patient died before its resolution. The overall mortality in the cohort was high at 58.2%. These findings corroborate the hypothesis that SIRPIDs might represent a state with increased epileptogenic potential, commonly co-occurring with NCSE. Furthermore, SIRPIDs are associated with therapy-refractory course of status epilepticus and high mortality.

Selective deep brain stimulation in the substantia nigra reduces myoclonus in progressive myoclonic epilepsy: a novel observation and short review of the literature.

We report the case of a patient suffering from pharmacotherapy-resistant bilateral progressive myoclonic epilepsy (PME) showing a beneficial response upon selective deep brain stimulation (DBS) of the substantia nigra pars reticulata. As an individual experimental therapeutic approach, we implanted DBS electrodes in the transitional zone between the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Electrode placement allowed for a selective stimulation of either the STN, SNr, or both targets. Postoperatively, we observed a moderate subjective and objective improvement in positive and negative myoclonus by high-frequency DBS of the STN/SNr transitional zone. However, a systematic exploration of different stimulation settings revealed that monopolar stimulation of the substantia nigra alone was more effective than high-frequency monopolar DBS of either the motor STN (monopolar) or stimulation of both targets (STN/SNr). This observation confirms earlier findings showing that patients with PME benefit from high-frequency DBS. However, in contrast to previous reports stimulating the STN/SNr transitional zone, our patient showed the most significant effect upon selective stimulation of the SNr. We propose that in patients undergoing DBS for myoclonus, at least one electrode contact should be placed in the SNr allowing for selective monopolar stimulation of this target.

Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+AT (Slc7a9) in mice.

Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 (rBAT) and SLC7A9 (b(0,+)AT). Gene targeting of the catalytic subunit (Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b(0,+). No remarkable gene expression changes were observed in other amino acid transporters and the peptide transporters in the intestine and kidney. Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout animals compared with wild-type animals. The fractional excretion of arginine was increased as expected (∼100%), but fractional excretions of lysine (∼35%), ornithine (∼16%), and cystine (∼11%) were less affected. Loss of function of b(0,+)AT reduced transport of cystine and arginine in renal BBMVs and completely abolished the exchanger activity of dibasic amino acids with neutral amino acids. In conclusion, loss of Slc7a9 function decreases the GFR and increases the excretion of several amino acids to a lesser extent than expected with no clear regulation at the mRNA and protein level of alternative transporters and no increased renal epithelial uptake. These observations indicate that transporters located in distal segments of the kidney and/or metabolic pathways may partially compensate for Slc7a9 loss of function.