Severe hypothalamopituitary dysfunction accompanied by influenza-associated encephalopathy: report of two pediatric cases.

Severe influenza infection may lead to neurological damage, such as encephalopathy. This may, in turn, cause acquired hypothalamopituitary dysfunction, which can result in severe morbidity and even death. We herein report two pediatric patients who developed influenza-associated hypopituitarism and were subsequently diagnosed with encephalopathy. They were diagnosed with acute necrotizing encephalopathy and postresuscitation encephalopathy, respectively. Both showed evidence of endocrine dysfunction, and hormone replacement therapy of adrenal, thyroid, and antidiuretic hormones are resulting in continued cardiac activity and resulted in prolonged survival. Screening for endocrine function is important in patients with severe central nervous system dysfunction.

A case of late-onset central hypoventilation syndrome with hypothalamic dysfunction: through a new phenotype.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder with uncertain nosology that usually presents early in life. The syndrome is characterized by ventilatory response impairment to carbon dioxide and may result in respiratory failure at birth. Recent reports have identified a similar clinical presentation beyond infancy called late-onset central hypoventilation syndrome (LO-CHS) as a disease continuum of CCHS with similar and overlapping pathophysiology. However, some have proposed that the syndrome accompanied by hypothalamic dysfunction (HD) be classified as a distinct clinical entity, LO-CHS/HD. To the best of our knowledge, the case reported herein is the oldest case of LO-CHS/HD in childhood, at 13 years old. He suffered from recurrent pulmonary edema, acute convulsive seizures, hypersomnia, hyperphagia, obesity, impaired glucose tolerance test, and hypercapnia, diagnosed as LO-CHS/HD, and was successfully treated with nasal bi-level positive airway pressure.

Bifid epiglottis: syndromic constituent rather than isolated anomaly.

BACKGROUND: Bifid epiglottis is a congenital malformation defined as a midline-cleft of the epiglottis, which can be presented as an isolated anomaly as well as a part of malformation complexes. Its common occurrence in Pallister-Hall syndrome (PHS) has recently been attracting special attention. In the embryo, epiglottis, hypothalamus, and digital buds develop synchronously. Some disturbances during this stage may account for the concurrence of bifid epiglottis, hypothalamic hamartoma, and polysyndactyly in PHS. The incidence of bifid epiglottis remains unknown. METHODS: We report here four children with bifid epiglottis out of 472 children who underwent laryngoscopy during the period from January 1995 to December 2004 in our hospital. RESULTS: All four children presented stridor of variable degrees. One had a partial cleft of the epiglottis associated with only tracheomalacia. The other three had a complete cleft of the epiglottis associated with complex malformations: one had accessory auricles with preauricular sinus, polycystic kidney disease with intrahepatic biliary dilatation, endocardial cushion defect, and postaxial polydactyly; another had hypothalamic hamartoma, Hirschsprung disease, and polydactyly, which warranted a diagnosis of PHS; the other had no other dysmorphic features. CONCLUSION: Bifid epiglottis can be presented as a syndromic constituent of congenital malformation syndromes rather than as an isolated anomaly. A high index of suspicion of bifid epiglottis should be raised in children with brachy-poly-syndactyly and clinical symptoms of upper airway obstruction.

Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome.

Prenatal exposure to alcohol has adverse effects on offspring neuroendocrine and behavioural functions. Alcohol readily crosses the placenta, thus directly affecting developing foetal endocrine organs. In addition, alcohol-induced changes in maternal endocrine function can disrupt the normal hormonal interactions between the pregnant female and foetal systems, altering the normal hormone balance and, indirectly, affecting the development of foetal metabolic, physiological and endocrine functions. The present review focuses on the adverse effects of prenatal alcohol exposure on offspring neuroendocrine function, with particular emphasis on the hypothalamic-pituitary-adrenal (HPA) axis, a key player in the stress response. The HPA axis is highly susceptible to programming during foetal and neonatal development. Here, we review data demonstrating that alcohol exposure in utero programmes the foetal HPA axis such that HPA tone is increased throughout life. Importantly, we show that, although alterations in HPA responsiveness and regulation are robust phenomena, occurring in both male and female offspring, sexually dimorphic effects of alcohol are frequently observed. We present updated findings on possible mechanisms underlying differential effects of alcohol on male and female offspring, with special emphasis on effects at different levels of the HPA axis, and on modulatory influences of the hypothalamic-pituitary-gonadal hormones and serotonin. Finally, possible mechanisms underlying foetal programming of the HPA axis, and the long-term implications of increased exposure to endogenous glucocorticoids for offspring vulnerability to illnesses or disorders later in life are discussed.

Hypothalamic hamartoma associated with a craniopharyngeal canal.

Hypothalamic hamartoma is a rare congenital lesion. We present the case of a 7-year-old girl who suffered from precocious puberty, the cause of which was diagnosed by using MR imaging and CT as pedunculated hypothalamic hamartoma associated with a large craniopharyngeal canal and sellar spine mimicking pituitary duplication.

Pre- and postnatal MR imaging of hypothalamic hamartomas associated with arachnoid cysts.

We describe two cases of hypothalamic hamartoma associated with arachnoid cysts. One case was initially documented on prenatal MR images. Because of the rarity of the association and resultant distortion in regional anatomy, the solid component of the mass may be overlooked. This would certainly be true when using lower-resolution diagnostic studies such as fetal MR imaging. The lesion could also be confused with a cystic tumor such as pilocytic astrocytoma. Thorough evaluation is required in patients with precocious puberty, gelastic seizures, and the presence of a suprasellar arachnoid cyst.

MR imaging and spectroscopy of a tuber cinereum hamartoma in a patient with growth hormone deficiency and hypogonadotropic hypogonadism.

To our knowledge, this is the first report of hypogonadotropic hypogonadism, or growth hormone deficiency, in a patient without non-Pallister-Hall syndrome who had hypothalamic hamartoma diagnosed on the basis of MR imaging and MR spectroscopy findings. On short-TE proton MR spectra, the N-acetylaspartate concentration in the hamartoma was lower than that in the thalamus but similar to that in the amygdala. However, myo-inositol concentration was elevated in the hamartoma compared with that in the amygdala and thalamus. This report stresses the advantages of short-TE spectroscopy and demonstrates that regional variations in spectra should be considered when reference structures are used.

Hypothalamic hamartoma and epilepsy in children: illustrative cases of possible evolutions.

The progresses of neuroimaging have allowed an earlier detection of hypothalamic hamartoma in children presenting with gelastic or dacrystic seizures. Associated symptoms can include other types of seizures, precocious puberty, and behavioral or cognitive deterioration. Combination of all these features is not constant and, when present, their evolution may be variable. When epilepsy proves intractable, surgery may be a solution but is not without risks. Therefore, it can only be justified on the basis of a considerable degree of certainty on the progressive character of the disorder, both in terms of epilepsy and global development. Even though epilepsy is a major and usually the most important problem, it is not always possible to predict its course and to be able to evaluate its potential effects on development. Available data suggests that deterioration is partly related to the epileptogenic activity. We reviewed data from 16 personal cases and discussed the possible evolutions of the epilepsy syndrome on the basis of 6 illustrative cases and a review of the literature. We point out that seizures may start early in life and evolve either towards a catastrophic encephalopathy or may be transiently severe and will progressively settle down. Intermediate situations also exist as well as cases presenting with a mild epilepsy. In almost all cases cognitive difficulties are present and may be associated with behavioral disturbances. They are of variable severity, usually in relation to the severity of the epilepsy and the evolution of the EEG abnormalities. Some of our cases also illustrate that, in young children whose seizures are limited to "a sensation of a pleasant feeling", "a pressure to laugh" or "smiling", early detection of the hamartoma may still be difficult and the epilepsy pattern may be misdiagnosed as an epilepsy temporal or frontal origin. Detailed analysis of the electro-clinical evolution of representative cases highlights the variable expression of the epilepsy syndrome and renders difficult any dogmatic position on early surgery. However, recent data suggests that a surgical solution must be sought early. Prospective studies are needed to evaluate, not only outcome in terms of control the seizures without unacceptable side effects but also on the evolution of the cognitive and behavioral profile of children with HH and epilepsy are needed.

Hamartoma of the suprasellar cistern in a 5-year-old girl.

A 5-year-old girl with precocious puberty secondary to a suprasellar hamartoma is presented. Magnetic resonance imaging (MRI) revealed a lesion without attachment to the tuber cinereum or the mamillary bodies. Total resection of the tumour was performed.

Recurrence of Pallister-Hall syndrome in two sibs.

We report the first definite sib recurrence of Pallister-Hall syndrome in a family without a cytogenetically visible chromosome abnormality. The father of these two sibs was born with nearly identical digital abnormalities and could represent either mild expression or gonosomal mosaicism for a dominant gene.

Female hypogonadotropic hypogonadism. Hypothalamic amenorrhea syndrome.

The neuroendocrine-metabolic repertoire governing the reproductive cyclicity in women can be interrupted by a variety of social, environmental, nutritional, and psychological aberrations. Clinical conditions including exercise-related and psychogenic amenorrhea, and desynchronization of biological rhythms in the development of hypothalamic gonadotropin-releasing hormone dysfunction are discussed. Clinical and laboratory evaluations and modes of management are presented.

New observations on midline defects: coincidence of anophthalmos, microphthalmos and cryptophthalmos with hypothalamic disorders.

Four children with severe congenital eye anomalies are described of which three had related symptoms. Two had bilateral anophthalmia, the optic nerves not detectable by computed cranial tomography and magnetic resonance imaging, and the third child had bilateral microphthalmia and coloboma iridis. The fourth patient had bilateral cryptophthalmia as part of Fraser syndrome. All four patients were of small stature. In three of them growth hormone deficiency was demonstrated which was of hypothalamic origin as shown by growth hormone releasing hormone tests. In the fourth child hypogonadotropic hypogonadism and tertiary thyroid deficiency were diagnosed which responded well to thyroxine treatment. Pathogenetically the described disorders are due to congenital defects of midline structures as a common "developmental field".