Kleine-Levin syndrome is a rare self-limited disorder which usually affects adolescent males and is characterized by episodic hypersomnia, increased appetite, and behavioral/psychiatric disturbances. Individuals are normal between the attacks.

The case of an adolescent boy is presented who suffered from recurrent sleepiness, hyperphagia, and behavioral disturbances such as rocking, punching and pacing, and was originally misdiagnosed as suffering from encephalitis. Before the diagnosis of Kleine-Levin was given, the patient underwent unnecessary investigations and treatment which, in turn, complicated his clinical condition both physically as well as psychologically. In the course of five years he had four such episodes which appeared to have progressively milder manifestations. Between episodes he was normal.

It is important that the diagnosis is suspected early, especially in adolescent males who present with recurrent episodes of somnolence, increased appetite, and abnormal behavior, since it most often represents a benign and self-limited entity and does not warrant extensive investigations or treatment. It is also important to distinguish this syndrome from more serious organic and psychiatric diseases with more serious prognoses. The differential diagnosis of this syndrome is discussed and a review of the literature is presented including evidence and hypotheses regarding its pathophysiology.

We have previously demonstrated that a sharp rise in feed intake (hyperphagia) and spontaneous liver steatosis could be experimentally induced in domestic Greylag geese by combining a short photoperiod and a sequence of feed restriction followed by ad libitum corn feeding during the fall and the winter. In this previous work, however, individual feed intake could not be recorded. The present study aimed at evaluating the relationship between level and pattern of hyperphagia and liver weight with an individual control of feed intake in individually housed (IH) geese, while comparing the performances with group housed (GH) geese. A total of 300 male geese of 19 weeks of age, were provided with corn ad libitum after an initial feed restriction period. From 21 to 23 weeks of age, the daylight duration was progressively reduced from 10 to 7 h and kept as such until the end of the experiment (week 36). In all, 30 GH and 30 IH geese were slaughtered at 19, 27, 30, 32 and 36 weeks of age. Feed intake was measured per group in GH geese and individually in IH geese. During the 1st week of corn feeding, the average feed intake rose up to 600 g/goose per day in GH geese but not in IH geese where the feed intake rose gradually from 300 to 400 g/day. The liver weight increased from 93 g (week 19) to 497 g (week 32; P<0.05) in GH birds. In IH birds, liver weights were, on average, much lower (ranging from 220 to 268 g) than in GH birds (P<0.05). In GH and IH bird, the variability in the individual response to corn feeding was very high (liver weight cv ranging from 63% to 83% depending on slaughter age). A close correlation between corn consumption and liver weight was evidenced in IH birds at each slaughter age (R2 ranging from 0.62 to 0.79), except at 36 weeks of age where this correlation was weak (R2=0.14). The variability in the extent of liver steatosis is very high and our results in IH birds clearly point out the major role of hyperphagia, mainly at the beginning of the ad libitum corn feeding period, on the development of spontaneous liver steatosis.

Rats are used as animal models in the study of antipsychotic-induced metabolic adverse effects, with oral drug administration yielding hyperphagia, weight gain and, in some cases, lipogenic effects. However, the rapid half-life of these drugs in rats, in combination with development of drug tolerance after a few weeks of treatment, has limited the validity of the model. In order to prevent fluctuating drug serum concentrations seen with daily repeated administrations, we injected female rats with a single intramuscular dose of long-acting olanzapine formulation. The olanzapine depot injection yielded plasma olanzapine concentrations in the range of those achieved in patients, and induced changes in metabolic parameters similar to those previously observed with oral administration, including increased food intake, weight gain and elevated plasma triglycerides. Moreover, the sensitivity to olanzapine was maintained beyond the 2–3 wk of weight gain observed with oral administration. In a separate olanzapine depot experiment, we aimed to clarify the role of hypothalamic AMP-activated protein kinase (AMPK) in olanzapine-induced weight gain, which has been subject to debate. Adenovirus-mediated inhibition of AMPK was performed in the arcuate (ARC) or the ventromedial hypothalamic (VMH) nuclei in female rats, with subsequent injection of olanzapine depot solution. Inhibition of AMPK in the ARC, but not in the VMH, attenuated the weight-inducing effect of olanzapine, suggesting an important role for ARC-specific AMPK activation in mediating the orexigenic potential of olanzapine. Taken together, olanzapine depot formulation provides an improved mode of drug administration, preventing fluctuating plasma concentrations, reducing handling stress and opening up possibilities to perform complex mechanistic studies.

Intrauterine growth-restricted (IUGR) offspring are at increased risk of adult obesity, as a result of changes in energy balance mechanisms. We hypothesized that impairment of hypothalamic insulin signaling contributes to hyperphagia in IUGR offspring. Study pregnant dams were 50% food restricted from days 10 to 21 to create IUGR newborns. At 5 weeks of age, food intake was measured following intracerebroventricular (icv) injection of vehicle or insulin (10 mU) in control and IUGR pups. At 6 weeks of age, with pups in fed or fasted (48 h) states, pups received icv vehicle or insulin after which they were decapitated, and hypothalamic arcuate (ARC) nucleus dissected for RNA and protein expression. IUGR rats consumed more food than controls under basal conditions, consistent with upregulated ARC phospho AMP-activated protein kinase (pAMPK) and neuropeptide Y (NPY). Insulin acutely reduced food intake in both control and IUGR rats. Consistent with anorexigenic stimulation, central insulin decreased AMP-activated protein kinase and NPY mRNA expression and increased proopiomelanocortin mRNA expression and pAkt, with significantly reduced responses in IUGR as compared with controls. Despite feeding, IUGR offspring exhibit a persistent state of orexigenic stimulation in the ARC nucleus and relative resistance to the anorexigenic effects of icv insulin. These results suggest that impaired insulin signaling contributes to hyperphagia and obesity in IUGR offspring.

The plasma glucose–insulin relationships and thyroid status were investigated in two lines of adult cockerels divergently selected for high (R+) or low (R-) residual food consumption (RFC). For a given body weight, R+ birds had a 74 % higher food intake than R- birds. Plasma glucose concentrations were significantly lower in the R+ line compared with the R- when fasted, whereas R+ birds exhibited a significantly lower plasma insulin concentration than R- birds either in fed or fasted state. After an overnight fast, R+ birds also exhibited a higher sensitivity to exogenous insulin in view of its more pronounced hypoglycaemic effect. After an oral glucose load, the glucose disposal of R+ cockerels was faster despite lower glucose-induced plasma insulin concentration. Whilst plasma triacylglycerol concentrations were lower in the R+ line when fed, plasma non-esterified fatty acid concentrations were higher in fasted R+ than R- cockerels (684 v. 522 μmol/l). Higher plasma triiodothyronine concentrations were observed in fed R+ compared with R- birds (3·0 v. 2·1 nmol/l respectively). The higher plasma concentrations of triiodothyronine associated with lower concentrations of insulin could account for the leanness and the elevated diet-induced thermogenesis previously observed in the R+ line.

This case report is of a young male with learning disability, who presented with long-term polydipsia and hyperphagia. The patient's polydipsia and hyperphagia showed a correlation with long-term use of neuroleptics for behavioural problems. Withdrawal of all neuroleptic medication resulted in an immediate improvement in both the polydipsia and hyperphagia leading to a complete resolution of both symptoms. While neuroleptics are a recognised cause of polydipsia, hyperphagia is less frequently described and we believe this to be the first report in which a patient is observed to have polydipsia and hyperphagia induced by neuroleptics. We discuss the possible aetiological mechanisms for both polydipsia and hyperphagia and conclude that the basic pathophysiology in our case appears to be a neuroleptic induced malfunction of the satiety centre due to blockage of dopamine receptors in the ventromedial hypothalamus.

Prader-Willi syndrome is a genetic illness associated with a defect on chromosome 15. It presents with hypotonicity in infancy followed by voracious appetite and gross obesity from early childhood and with a range of other clinical and behavioural sequelae. This case report is of an adolescent boy who was admitted to a psychiatric unit for an intensive behavioural programme to control his weight gain and deal with associated behavioural problems, and demonstrates that an inpatient programme can lead to sustainable improvements in weight control and other indicators of well-being in PWS patients.