4.

Object The Dandy–Walker complex is a continuum of aberrant development of the posterior fossa that has been associated with multiple congenital anomalies, radiographic abnormalities, and developmental delay. The Dandy–Walker variant (DWV) is a unique entity believed to represent a milder form of the complex, and is characterized by a specific constellation of radiographic findings. In this retrospective case series, the authors report the association of the DWV with other congenital anomalies, the associated radiographic findings linked with DWV, and the developmental outcome in this population. Methods The charts and radiographs of 10 male and 14 female patients treated between 2000 and 2006 were examined. The patients' mean gestational age was 35.6 weeks (range 23–41 weeks), and the mean follow-up period was 5.1 years (range 1 month–15 years). Results Three patients died. Associated anomalies included cardiac (41.7%), neurological (33.3%), gastrointestinal (20.8%), orthopedic (12.5%), and genitourinary (12.5%) abnormalities. Less common were pulmonary and psychiatric findings. Developmental delay was identified in 11 of the 21 patients for whom follow-up was available. Five of 6 patients with isolated DWV had a normal developmental course. Radiographic findings associated with DWV included corpus callosum dysgenesis in 20.8%, ventricular enlargement in 29%, and vermian rotation in 8.3%. Shunts were placed in 4 of 7 patients with ventriculomegaly. Using the two-tailed Pearson correlation, the authors determined that developmental outcome was solely affected by neurological deficits and that ventricular enlargement predicted the need for shunt placement. Conclusions The DWV was associated with both extra- and intracranial anomalies. Associated radiographic abnormalities including ventriculomegaly were observed. Hydrocephalus requiring cerebrospinal fluid diversion may be indicated. Isolated DWV was associated with a good developmental outcome.

These studies addressed the question of serotonin (5-HT)-dopamine (DA) interactions with regard to reward-related behavior and motor activity in rats. The first experiment evaluated the effect of chronic treatment with fluoxetine (7 mg/kg/day), a serotonin-selective reuptake inhibitor, and buproprion (15 mg/kg/day), a dopamine reuptake inhibitor, on responding for conditioned reinforcement (CR). Chronic fluoxetine, but not buproprion, enhanced CR responding, and also potentiated cocaine-induced increases in CR responding. In the second experiment, animals received intra-accumbens infusions of either 1, 5, and 10 g) or DA (10, 20 g) The dopaminergic and serotonergic neurotransmitter systems are thought to play a critical role in the regulation of emotion and mood, and have been implicated in a spectrum of neuropsychiatric disorders. Psychotropic drugs affecting dopaminergic or serotonergic systems have been used to treat such disorders as depression, bipolar disorder, schizophrenia, eating disorders, obsessive compulsive disorder, and autism and have also been used to alleviate motor dysfunction associated with Tourette's syndrome, Parkinson's disease, and self-injurious behavior. Since both these transmitter systems appear to play such a critical role in mental functions, there has been a considerable amount of interest in their potential interactions. The nucleus accumbens, which has been implicated in reward and motivation, is one brain region where such an interaction may take place. There are high levels of dopamine (DA), dopamine receptors, serotonin (5-HT), and serotonin receptors in this forebrain region (Beal and Martin 1985;Bonaventure et al. 1997;Bouyer et al. 1984;Eberle-Wang et al. 1997;Joyce and Marshall 1987;Kilpatrick et al. 1987; Phelix and Broderick 1995;. The classical role of dopamine in the nucleus accumbens has been attributed to regulating motivation and reward-related behavior (Robbins and Everitt 1996;Schultz 1997;Wise and Rompré 1989). For example, drugs of abuse, such as cocaine and amphetamine, are believed to exert their euphoric effects primarily via activating the dopamine system (Di Chiara and Imperato 1988; Koob and Bloom 1988). In contrast to the substantial body of research on dopamine in the nucleus accumbens, there has been comparatively little attention given to the role of serotonin and serotonin-dopamine interactions in the nucleus accumbens.There are a number of reasons why further understanding of dopamine-serotonin interactions would be useful. Although depression undoubtedly involves a complex dysregulation of many transmitter and neuroendocrine systems, a majority of drugs used to treat depression affects the serotonin system. Serotoninselective re-uptake inhibitors (SSRIs) such as fluoxetine enhance synaptic levels of serotonin (5-HT), and are generally quite effective in ameliorating the symptoms of depression. Thus, one widely held hypothesis is that dysfunction in serotonergic neurons and their targets may underlie depressive symptomatology (van Praag et al. 1...

Stereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

EEAs to ITF tumors are technically feasible with low risk of complications for well-selected patients. The proposed classification system is useful for anticipating potential sequelae for each approach.