Low resolution electromagnetic tomography analysis of ictal EEG patterns in mesial temporal lobe epilepsy with hippocampal sclerosis

ObjectiveTo investigate the difference in the spatial distribution of scalp initial ictal discharge (IID) patterns in mesial temporal lobe epilepsy with hippocampal sclerosis (HS–MTLE).MethodsScalp ictal EEG data in 22 seizure-free patients after temporal lobectomy with amygdalo-hippocampectomy were classified as follows: a regular 5–9 Hz rhythm with a restricted temporal/subtemporal distribution (type 1, 11 patients), or an irregular 2–5 Hz rhythm with a widespread fronto-temporal distribution (type 2, 11 patients). EEG data were fragmented into segments of 1.28 s, both at ictal onset and at baseline. The LORETA solution of three frequency bands was compared between ictal and baseline using statistical non-parametric mapping (p < 0.01).ResultsThe LORETA solution of 5–9 Hz in type 2 had wider cortical activity in the ipsilateral fronto-temporal area, compared to type 1 with activation of the ipsilateral focal mesial and lateral temporal regions. The LORETA solution of 10–13 Hz in both types showed increased activity in the fronto-temporal area, which was wider in type 2 than type 1. Increased cortical activity of <5 Hz was not observed in type 1, whereas increased cortical activity was observed in the bilateral anterior frontal area in type 2.ConclusionsThe cortical source distribution in HS–MTLE may depend on scalp IID frequency. The neural generators of 5–13 Hz may be important for the formation of the ictal onset zone in both ictal patterns.SignificanceSpatial distributions in HS–MTLE patients differ with scalp IID frequency.     

Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging

Purpose

The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model.

Methods

Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks).

Results

In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p?=?0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p?=?0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p?=?0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p?=?0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p?Conclusions All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.     

Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease

Background and Objective: Prasugrel is a thienopyridine antiplatelet agent under investigation for the prevention of atherothrombotic events in patients with acute coronary syndrome who undergo percutaneous coronary intervention. Patients with chronic liver disease are among those in the target population for prasugrel. As hepatic enzymes play a key role in formation of prasugrel’s active metabolite, hepatic impairment could affect the safety and/or efficacy of prasugrel in such patients. Methods: This was a parallel‐design, open‐label, multiple dose study of 30 subjects, 10 with moderate hepatic impairment (Child‐Pugh Class B) and 20 with normal hepatic function. Prasugrel was administered orally as a 60‐mg loading dose (LD) and daily 10‐mg maintenance doses (MDs) for 5 days. Pharmacokinetic parameters (AUC_0–t, C_max and t_max) and maximal platelet aggregation (MPA) by light transmission aggregometry were assessed after the LD and final MD. Results and Discussion: Exposure to prasugrel’s active metabolite was comparable between healthy subjects and those with moderate hepatic impairment. Point estimates for the ratios of geometric least square means for AUC_0–t and C_max after the LD and last MD ranged from 0·91 to 1·14. MPA to 20 μm ADP was similar between subjects with moderate hepatic impairment and healthy subjects for both the LD and MD. Prasugrel was well tolerated by all subjects, and adverse events were mild in severity. Conclusion: Moderate hepatic impairment appears to have no effect on exposure to prasugrel’s active metabolite. Furthermore, MPA results suggest that moderate hepatic impairment has little or no effect on platelet aggregation relative to healthy controls. Overall, these results suggest that a dose adjustment would not be required in moderately hepatically impaired patients taking prasugrel.     

Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease

Objective:  The pharmacokinetic (PK) and pharmacodynamic (PD) responses to prasugrel were compared in three studies of healthy subjects vs. those with moderate or end-stage renal impairment.
Methods:  Two of the three protocols were parallel-design, open-label, single dose (60-mg prasugrel) studies in subjects with end-stage renal disease (ESRD; n  = 12) or moderate renal impairment ( n  = 10) and matched healthy subjects with normal renal function ( n  = 10). The third protocol was an open-label, single-dose escalation (5, 10, 30 and 60 mg prasugrel) study in subjects with ESRD ( n  = 16) and matched healthy subjects with normal renal function ( n  = 16). Plasma concentrations of prasugrel's active metabolite were determined and pharmacokinetic parameter estimates were derived. Maximum platelet aggregation (MPA) was measured by light transmission aggregometry using 20 μ m adenosine diphosphate as agonist.
Results:  Across all studies, prasugrel's C _max and AUC_{0– t} were 51% and 42% lower in subjects with ESRD than in healthy subjects. AUC_{0– t} did not differ between healthy subjects and subjects with moderate renal impairment. The magnitude of change and time-course profiles of MPA was similar for healthy subjects compared with subjects with moderate renal impairment and those with ESRD. Prasugrel was well-tolerated in all subjects.
Conclusion:  There was no difference in pharmacokinetics or PD responses between subjects with moderate renal impairment and healthy subjects. Despite significantly lower exposure to prasugrel's active metabolite in subjects with ESRD, MPA did not differ between healthy subjects and those with ESRD.     

Dexmedetomidine for awake fiberoptic intubation in a parturient with spinal muscular atrophy type III for cesarean delivery

Spinal muscular atrophy in pregnancy is rare and poses multiple problems for the anesthesiologist. The effects of dexmedetomidine on a parturient with spinal muscular atrophy have not previously been reported. There are also no in vivo data on placental transfer of dexmedetomidine and its effects on a human neonate. We report the hemodynamic, respiratory and sedative effects of dexmedetomidine on a parturient and neonate when used for awake fiberoptic intubation before cesarean section. A 35-year-old, gravida 4 para 0 aborta 3, 41-kg parturient at 35 weeks of gestation with spinal muscular atrophy presented for cesarean section. Dexmedetomidine was administered intravenously, total dose 1.84 μg/kg over 38 minutes, followed by fiberoptic endotracheal intubation. Dexmedetomidine was then discontinued and general anesthesia was induced. The baby was delivered 68 minutes after the dexmedetomidine infusion was discontinued at which time blood samples were obtained for measurement of dexmedetomidine. During administration of dexmedetomidine, maternal heart rate, blood pressure and oxygen saturation remained stable. Apgar scores at 1 and 5 min were 6 and 8. The fetal concentration of dexmedetomidine (540 pg/mL) indicates significant placental transfer, but significant adverse neonatal effects were not observed. Dexmedetomidine alone provided adequate sedation for awake intubation without respiratory compromise in this patient.