Studying Placozoa WBR in the Simplest Metazoan Animal, Trichoplax adhaerens.

Placozoans are a promising model system to study fundamental regeneration processes in a morphologically and genetically very simple animal. We here provide a brief introduction to the enigmatic Placozoa and summarize the state of the art of animal handling and experimental manipulation possibilities.

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

OBJECTIVE: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs). METHODS: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs. RESULTS: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers. CONCLUSIONS: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.

Dynamic FoxP2 levels in male zebra finches are linked to morphology of adult-born Area X medium spiny neurons.

The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. FOXP2 mutations are associated with specific speech and language impairments. In songbirds, experimentally altered FoxP2 expression levels in the striatal song nucleus Area X impair vocal learning and song production. Overall FoxP2 protein levels in Area X are low in adult zebra finches and decrease further with singing. However, some Area X medium spiny neurons (MSNs) express FoxP2 at high levels (FoxP2high MSNs) and singing does not change this. Because Area X receives many new neurons throughout adulthood, we hypothesized that the FoxP2high MSNs are newly recruited neurons, not yet integrated into the local Area X circuitry and thus not active during singing. Contrary to our expectation, FoxP2 protein levels did not predict whether new MSNs were active during singing, assayed via immediate early gene expression. However, new FoxP2high MSNs had more complex dendrites, higher spine density and more mushroom spines than new FoxP2low MSNs. In addition, FoxP2 expression levels correlated positively with nucleus size of new MSNs. Together, our data suggest that dynamic FoxP2 levels in new MSNs shape their morphology during maturation and their incorporation into a neural circuit that enables the maintenance and social modulation of adult birdsong.

Seizure detection watch improves quality of life for adolescents and their families.

This article reports the findings from a pilot study conducted to explore the impact of using a wearable seizure detection device on quality of life for 10 adolescents with epilepsy and their parents. Quality of life in Epilepsy for Adolescent (QOLIE AD-48) and the Parent Response to Child Illness (PRCI) Scale were compared at study onset and 6 months after using the SmartWatch seizure detection device. At the conclusion of the study, a qualitative interview explored the adolescent's and parent's experiences with using the device. In this sample, the wearable seizure detection device was well accepted as a means to increase seizure safety for both adolescents and their caregivers. In addition, adolescents and parents felt more secure with the adolescent increasing independent activities when wearing the watch. Barriers to use included technical difficulties, such as false alarms, and the burden of adding another aspect to their epilepsy care. While these data cannot be generalized to all populations, findings suggest that further research with wearable seizure detection devices is warranted. Considering current sudden unexplained death from epilepsy (SUDEP) prevention guidelines that encourage seizure monitoring, especially during sleep, the wearable seizure detection device may provide adequate seizure monitoring without the negative consequences to the adolescent's developing autonomy.

Maturation, Behavioral Activation, and Connectivity of Adult-Born Medium Spiny Neurons in a Striatal Song Nucleus.

Neurogenesis continues in the adult songbird brain. Many telencephalic song control regions incorporate new neurons into their existing circuits in adulthood. One song nucleus that receives many new neurons is Area X. Because this striatal region is crucial for song learning and song maintenance the recruitment of new neurons into Area X could influence these processes. As an entry point into addressing this possibility, we investigated the maturation and connectivity within the song circuit and behavioral activation of newly generated Area X neurons. Using BrdU birth dating and virally mediated GFP expression we followed adult-generated neurons from their place of birth in the ventricle to their place of incorporation into Area X. We show that newborn neurons receive glutamatergic input from pallial/cortical song nuclei. Additionally, backfills revealed that the new neurons connect to pallidal-like projection neurons that innervate the thalamus. Using in situ hybridization, we found that new neurons express the mRNA for D1- and D2-type dopamine receptors. Employing DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa) and EGR-1 (early growth response protein 1) as markers for neural maturation and activation, we established that at 42 days after labeling approximately 80% of new neurons were mature medium spiny neurons (MSNs) and could be activated by singing behavior. Finally, we compared the MSN density in Area X of birds up to seven years of age and found a significant increase with age, indicating that new neurons are constantly added to the nucleus. In summary, we provide evidence that newborn MSNs in Area X constantly functionally integrate into the circuit and are thus likely to play a role in the maintenance and regulation of adult song.

The relationship between the Neuro-Quality of Life Depression and Anxiety Measures and the Personality Assessment Inventory in persons with epilepsy.

BACKGROUND: To investigate the associations between the Neuro-Quality of Life (NQOL) Depression and Anxiety measures with an objective emotional inventory (Personality Assessment Inventory; PAI), and demonstrate the clinical utility of the NQOL as screening measures for depression and anxiety in persons with epilepsy (PWE). METHODS: PWE (N=72) were concurrently administered the NQOL Depression and Anxiety measures and the PAI. Pearson product moment correlations were used to determine the relationships between the NQOL measures and the respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted comparing NQOL scores between patients with elevated levels of depression and anxiety (T-score≥65 on the PAI) to profiles that were within normal limits. Using sensitivity and specificity analyses, optimal cut-scores on the NQOL measures were determined. RESULTS: Participants were primarily Caucasian (89%), female (60%), and ~35 years old. The NQOL Depression measure was significantly correlated with the PAI Depression total score (r=.747; p<0.001) and its subscales (p's<0.001). Similarly, the NQOL Anxiety measure was significantly correlated with the PAI Anxiety total score (r=.750; p<0.001) and its subscales (p's<0.001). Compared to profiles that were within normal limits, individuals with elevated depressive symptoms on the PAI had significantly higher NQOL Depression scores (F(1,71)=48.2, p<0.001, d=1.6). Similarly, those who endorsed elevated anxiety on the PAI had significantly higher NQOL Anxiety scores (F(1,71)=32.2, p<0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and 24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67; specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77; specificity=0.82; PPV=0.81; NPV=0.78) in PWE. CONCLUSIONS: The NQOL Depression and Anxiety measures evidenced strong associations with the PAI Depression and Anxiety scales and may be effective in detecting depressive and anxiety symptoms in PWE using the provided cut-scores.

Measuring preoperative anxiety in patients with breast cancer using the visual analog scale.

Preoperative anxiety is a prevalent concern with deleterious effects in patient recovery and is not routinely assessed in the preoperative screening process. When it is assessed, it may prompt an increase in the use of anesthetic agents, heightened postoperative pain, and prolonged hospitalization. Preoperative women with breast cancer face anxiety as it relates to anesthesia, surgery, and recovery. The preoperative anxiety visual analog scale may identify and quantify anxiety in this population, provide advocacy and support, and improve the preoperative screening process.

A retrospective observational study of current treatment for generalized convulsive status epilepticus.

OBJECTIVES: This study aimed at determining the current state of practice of treatment for acute generalized convulsive status epilepticus (GCSE) and responsiveness to therapy. METHODS: This observational study was performed by retrospectively identifying patients with GCSE presenting to an emergency room setting. The primary outcome was seizure cessation following medication administration. Secondary outcomes were rates of intubation and mortality. RESULTS: One hundred seventy-seven episodes of GCSE were identified. All patients, except 1, received a benzodiazepine for first-line treatment. Only 11% of these patients, all children, were treated with at least 0.1mg/kg of lorazepam or an equivalent dose of an alternative benzodiazepine. A first-line treatment was effective in 56% of the patients, a second-line treatment in an additional 28%, and a third-line treatment in 12%. Phenytoin was the most prescribed second-line treatment (41%) but statistically significantly least effective (22% versus 86% seizure cessation, p<0.0001) compared with all other second-line agents together. Propofol was the most prescribed third-line treatment. CONCLUSIONS: Results emphasize that, in clinical practice, approximately half of GCSE patients respond to first-line therapy and, among nonresponders, approximately two-thirds respond to second-line and approximately three-quarters respond to third-line therapies. The variations in treatment selection reflect that there are no randomized controlled trials to guide treatment beyond use of benzodiazepines for first-line treatment. The observation that phenytoin is statistically substantially worse than other second-line treatments raises the possibility that the most commonly selected second-line treatment is the least effective and provides equipoise for a large randomized controlled trial of second-line therapies.

An unusual presentation of anti-Hu-associated paraneoplastic limbic encephalitis.

Paraneoplastic limbic encephalitis is a rare disorder characterized by personality changes, seizures, memory loss, and psychiatric symptoms often associated with antineuronal antibodies. It is well described in the adult literature but is still underreported in the pediatric literature. Symptoms are usually multifocal and subacute in presentation, occurring over days to weeks; however, in rare cases, symptom onset can be more gradual. We report the case of a 9-year-old male with anti-Hu-associated paraneoplastic limbic encephalitis that presented as episodic ataxia and behavioral changes evolving to intractable epilepsy and worsening behavioral changes over the course of a year. This case highlights the importance of considering a paraneoplastic disorder in the differential diagnosis for unexplained multifocal neurological symptoms of subacute or chronic onset as earlier detection and treatment may result in an improved outcome.

Extrapontine myelinolysis resulting in transient cortical blindness.

Central pontine myelinolysis and extrapontine myelinolysis are characterized by symmetric demyelination subsequent to rapid shifts in serum osmolality. Described here is a novel case of transient cortical blindness in association with imaging features of extrapontine myelinolysis, which occurred in a child with carbamoyl phosphate synthetase deficiency after rapid correction of hyperammonemia. Serum sodium levels were within normal limits at presentation and throughout the period of ammonia correction. A potential pathogenic mechanism of osmotic demyelination in the setting of acute treatment for hyperammonemia in a patient with a urea cycle abnormality includes disruption of the blood-brain barrier and re-equilibration of organic osmolytes, particularly glutamine.