Psychiatric comorbidity with hypothalamic hamartoma: Systematic review for predictive clinical features.

OBJECTIVE: We conducted a systematic review of the English-language literature to identify clinical features associated with a higher risk of psychiatric symptoms (aggression and rage behaviors) in patients with hypothalamic hamartoma (HH) and epilepsy. METHODS: Two publicly-accessible databases (PubMed and Cochrane Library) were searched for Hypothalamic Hamartoma AND Epilepsy. We identified peer-reviewed original research publications (case reports or clinical series; N=19) in which clinical data was provided on an individual basis. Subjects were cohorted into those with (N=51) and without (N=68) behavioral aggression. Multiple clinical features were collated and subjected to univariate analysis to determine possible differences between these two cohorts. RESULTS: The presence of aggression significantly correlated with 1) male gender, 2) younger age at time of first seizure onset, 3) the presence of intellectual disability, and 4) the presence of multiple seizure types (versus gelastic seizures only). For those patients undergoing surgical treatment, aggression also correlated with younger age at the time of surgical intervention. CONCLUSION: Possible predictive clinical features for the presence of aggression and rage behaviors in patients with hypothalamic hamartoma and epilepsy are identified. These results may contribute to the complex treatment decisions that are unique to this population.

Synthesis and biological evaluation of 11' imidazolyl antiprogestins and mesoprogestins.

Antiprogestins with a 4' para imidazolylphenyl moiety were synthesized and their biochemical interactions with the progesterone and glucocorticoid receptor were investigated. Depending on the substitution pattern at the 17 position partial progesterone receptor (PR)-agonistic derivatives like compounds EC339 and EC336 or pure antagonists like compound EC317 were obtained. EC317 was investigated in vivo and found to be significantly more potent than RU 486 in cycling and pregnant guinea pigs. For testing the biological action progesterone receptor modulators (PRM), guinea pigs appears as a specific model when compare to pregnant human uterus. This model correlates to human conditions such as softening and widening of the cervix, the elevation of the uterine responsiveness to prostaglandins and oxytocin, and finally to induction of labor. The use of non-pregnant guinea pigs permitted the simultaneous assessment of PR-agonistic and PR-antagonistic properties and their physiological interactions with uterine and vaginal environment. These can histologically be presumed from the presence of estrogen or progesterone dominance in the genital tract tissues. The ovarian histology indicated the effects on ovulation. Corpora lutea in guinea pigs further reflects inhibitory effects of the progesterone-dependent uterine prostaglandin secretion. PRMs are initially synthesized as analogues of RU 486. They represent a heterogeneous group of compounds with different ratios of PR-agonistic and-antagonistic properties. PR-agonistic properties may be essential for uterine anti-proliferative effects. In various clinical studies these were also attributed to RU 486 or Ulipristal [1,2]. Adjusted PR-agonistic PRMs (EC312, EC313) [3] may be more effective in achieving a mitotically resting endometrium and superior uterine tumor inhibition. For the use in termination of pregnancy, progesterone-inhibitory effects are essentially needed. Even minor PR-agonistic properties compromise the therapeutic goals. Pure PR-antagonists, as EC317, clearly exceeded the gold standard RU 486 with respect to labor inducing effects. Mechanistically it is surprising that both types of compound may be potent inhibitors of ovulation.