Early thalamic lesions in patients with sleep-potentiated epileptiform activity.

OBJECTIVE: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). METHODS: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. RESULTS: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). CONCLUSIONS: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.

Altered fetal cerebral and cerebellar development in twin-twin transfusion syndrome.

BACKGROUND AND PURPOSE: Neurodevelopmental disability is common in twins with TTTS in utero; however, the responsible neuropathology remains uncertain. We proposed to document the frequency of brain abnormalities on clinical fetal MR images and to determine if quantitative fetal brain biometric analysis in twin fetuses with TTTS was different from those in healthy control fetuses. MATERIALS AND METHODS: We reviewed the fetal brain MR images of 33 twin pairs with TTTS clinically evaluated in our institution. Eighteen fetal MR images of "healthy" twins with TTTS were further studied with biometric analysis in comparison with GA-matched singleton fetuses to detect quantitative differences in brain growth and development. RESULTS: A higher incidence of anomalies (11/33, 33.3%) was found than previously reported. The most frequent abnormality was ventriculomegaly (7/11, 63%) in both donor and recipient. In "healthy" twins with TTTS, biometric analysis revealed persistently small measurements (cBTD, CMT, TCD, and VAPD) in the donor cerebrum and cerebellum in comparison with their recipient cotwin and healthy control fetuses. These differences were preserved when normalized by cBTD. CONCLUSIONS: Our findings show that significant brain abnormalities are common in TTTS. In addition, diffuse subtle abnormalities are also present in normal-appearing donor fetal brains that cannot be solely explained by overall growth restriction. Such subtle fetal brain anomalies may explain the high incidence of poor long-term neurodevelopmental outcomes of survivors, and they need to be further investigated with more sophisticated quantitative fetal imaging methodologies.

Brain perfusion in asphyxiated newborns treated with therapeutic hypothermia.

BACKGROUND AND PURPOSE: Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term neonates. The purpose of this study was to assess brain perfusion in the first week of life in these neonates. MATERIALS AND METHODS: In this prospective cohort study, MR imaging and ASL-PI were used to assess brain perfusion in these neonates. We measured regional CBF values on 1-2 MR images obtained during the first week of life and compared these with values obtained in control term neonates. The same or later MR imaging scans were obtained to define the extent of brain injury. RESULTS: Eighteen asphyxiated and 4 control term neonates were enrolled; 11 asphyxiated neonates were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on DOL 1 and then hyperperfusion on DOL 2-3 in brain areas subsequently exhibiting injury. Asphyxiated neonates not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1-6 in brain areas displaying injury. CONCLUSIONS: Our data show that ASL-PI may be useful for identifying asphyxiated neonates at risk of developing brain injury, whether or not hypothermia is administered. Because hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such neonates may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies.

Circadian patterns of pediatric seizures.

OBJECTIVE: To evaluate the relationship of sleep/wake and day/night pattern to various seizure subtypes and epilepsy localizations. METHODS: Charts of 380 consecutive pediatric patients with epilepsy undergoing video-EEG (V-EEG) over 2 years were reviewed for seizure semiology, EEG localization, occurrence during the day (6 am-6 pm) or night, during wakefulness and sleep, 3-hour time blocks throughout 24 hours, and various epilepsy localizations, and etiology. RESULTS: A total of 1,008 seizures were analyzed in 225 children (mean age 8.5 ± 5.7 years). Sleep and wakefulness predicted seizure semiology and localization more reliably than daytime and nighttime. Auras, gelastic, dyscognitive, atonic, hypomotor, and myoclonic seizures, and epileptic spasms occurred more often in wakefulness, while tonic, tonic-clonic, automotor, and hypermotor seizures occurred more frequently in sleep (p < 0.05). Clonic, atonic, myoclonic, and hypomotor seizures occurred more frequently during daytime. Hypermotor and automotor seizures occurred more frequently at night (p < 0.05). Generalized seizures (6 am-12 pm), temporal lobe seizures (9 pm-9 am), frontal lobe seizures (12 am-6 am), parietal lobe seizures (6 am-9 am), and occipital lobe seizures (9 am-noon and 3-6 pm) revealed specific circadian patterns (p < 0.05). In addition, generalized and temporal lobe seizures occurred more frequently in wakefulness, while frontal and parietal seizures occurred more frequently in sleep, independent of day or night pattern (p < 0.05). CONCLUSION: Sleep and wakefulness, as well as time of day and night, are important considerations in proper characterization of seizure types and epilepsy localization. These findings may contribute to a better understanding of the mechanisms of nonrandom distribution of seizures, and may provide information for individualized treatment options.

Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease.

BACKGROUND: Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated. OBJECTIVE: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. METHODS: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. RESULTS: Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy. CONCLUSIONS: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. .

Effect of periovulatory prostaglandin F2alpha on pregnancy rates and luteal function in the mare.

The objective of this study was to determine whether periovulatory treatments with PGF2alpha affects the development of the CL, and whether the treatment was detrimental to the establishment of pregnancy. Reproductively sound mares were assigned randomly to one of the following treatment groups during consecutive estrus cycles: 1. 3,000 IU hCG within 24 hours before artificial insemination and 500 microg cloprostenol (PGF2alpha analogue) on Days 0, 1, and 2 after ovulation (n=8), 2. 2 mL sterile water injection within 24 hours before artificial insemination and 500 microg cloprostenol on Days 0, 1, and 2 after ovulation (n=8); 3. 3,000 IU hCG within 24 hours before artificial insemination and 500 microg cloprostenol on Day 2 after ovulation (n=8); or 4. 3,000 IU hCG within 24 hours before artificial insemination and 2 mL of sterile water on Days 0, 1, and 2 after ovulation (controls; n=8). Blood samples were collected from the jugular vein on Days 0, 1, 2, 5, 8, 11, and 14 after ovulation. Plasma progesterone concentrations were determined by the use of a solid phase 125I radioimmunoassay. All mares were examined for pregnancy by the use of transrectal ultrasonography at 14 days after ovulation. Mares in Group 1 and 2 had lower plasma progesterone concentrations at Day 2 and 5, compared to mares in the control group (P < 0.001). No difference was detected between group 1 and 2. Plasma progesterone concentrations in group 3 were similar to the control group until the day of treatment, but decreased after treatment and were significantly lower than the control group at Day 5 (P < 0.001). Plasma progesterone concentrations increased in all treatment groups after Day 5, and were comparable among all groups at Day 14 after ovulation. Cloprostenol treatment had a significant effect on pregnancy rates (P < 0.01). The pregnancy rate was 12.5% in Group 1, 25% in Group 2, 38% in Group 3, and 62.5% in Group 4. It was concluded that periovulatory treatment with PGF2alpha has a detrimental effect on early luteal function and pregnancy.