Hypothalamic Lesions Research Articles

OR16-3 Posterior Hypothalamus-Sparing Surgery Improves Outcome after Childhood Craniopharyngioma: Results of the Prospective Multinational Trial Kraniopharyngeom 2007

Background: Quality of survival (QoS) is frequently impaired in childhood-onset craniopharyngioma (CP) patients by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or treatment-related hypothalamic lesions (HL) determine outcome, is controversial. Methods: In cross-sectional prospective study, survival and outcome of 109 CPs recruited 2007-2014 in KRANIOPHARYNGEOM 2007 with reference-confirmed presurgical, anterior and posterior HI were analyzed with regard to surgical HL (no, anterior or anterior and posterior HL). Body mass index (BMI), QoS assessed by PEDQOL, and functional capacity (FMH) were measured at diagnosis, during follow-up, and at last visit (median follow-up: 6 years). Results: Surgical HL were reference-confirmed in 86 of 109 (79%) CP (29 anterior, 57 anterior and posterior HL). PFS and BMI at diagnosis were similar in CP subgroups with different degree of HL. CP with anterior and posterior HL presented with higher BMI at one-year follow-up (median BMI: +5.21 SD) and at last visit (BMI: +5.74 SD), when compared to patients without HL (BMI, one year: +1.72 SD, p=0.001; last visit BMI: +2.27 SD, p<0.001) and when compared to patients with anterior HL (BMI, 1 year: +2.46 SD, p=0.002; last visit: +2.87 SD, p=0.001). QoS improved during follow-up in CP without HL for physical functionality (p=0.047), emotional stability (p=0.040), and social functionality (p=0.002) when compared to CP with anterior and posterior HL. Functional capacity was not associated with degree of HL. Conclusions: Based on appropriate preoperative staging, posterior hypothalamus-sparing surgical strategies do not increase risk for relapse/progression, improve QoS and ameliorate development of obesity in CP at risk for obesity due to presurgical anterior and posterior HI.

MON-443 Periostin Concentrations in Childhood-Onset Craniopharyngioma Patients

Objective: The extracellular matrix protein periostin is highly expressed in adamantinomatous craniopharyngioma-associated fibroblasts. Periostin has been further identified as a novel marker for Non-Alcoholic Fatty Liver Disease (NAFLD). Half of childhood-onset craniopharyngioma patients (CP) with hypothalamic syndrome develop NAFLD. We hypothesized that periostin concentration is elevated in biological fluids of CP and associated with pathological hepatic parameters, indicating increased risk for NAFLD. Design: Cross-sectional study on patients with sellar masses (SMP) recruited in the German Craniopharyngioma Registry. Patients: 35 SMP (32 CP, 2 xanthogranuloma, one pilocytic astrocytoma), 3 short-statured patients with isolated growth hormone deficiency (GHD), 5 short-statured patients with normal findings in GH stimulating tests and decreased insulin-like growth factor (IGF)-1 (IGF-1D) and 7 healthy controls. Measurements: Periostin concentrations were measured by Elisa in serum (32 CP, 2 xanthograuloma, 3 GHD, 5 IGF-1D and 7 healthy controls), urine (27 CP, 3 GHD, 5 IGF-1D, 7 healthy controls) and saliva (18 CP, 3 GHD, 3 IGF-1D, 7 healthy controls). Results: Periostin serum, urine and saliva concentrations in CP were similar to concentrations of the other groups. Hypothalamic involvement/hypothalamic lesions, degree of obesity (BMI SDS) as well as hepatic enzymes were not associated with elevated periostin concentrations. Due to low patient numbers with pathological hepatic parameters, missing imaging data on the degree of steatosis hepatis and the lack of histological proof of NAFLD no definitive conclusions can be drawn from measured periostin concentrations in serum. Interestingly, the subgroup of patients with decreased IGF-1 levels showed elevated concentrations of serum periostin when compared with other groups. Conclusions: Periostin concentrations in biological fluids of CP are not associated with known risk factors for NAFLD such as hepatic and metabolic parameters, obesity and hypothalamic lesions. Accordingly, periostin does not seem to be a suitable marker for NAFLD in childhood-onset CP. The association between decreased IGF-1 and increased periostin concentrations should be part of further investigation.

SAT-428 Effect of Age, Body Mass Index, and Sex on the Performance of Macimorelin for the Diagnosis of Adult Growth Hormone Deficiency: A Post Hoc Analysis

Background: The diagnostic performance of macimorelin (MAC), an orally active ghrelin receptor agonist approved for the diagnosis of adult growth hormone deficiency (AGHD) in the United States, has previously been demonstrated in a phase 3 study that compared MAC with the insulin tolerance test (ITT).1 However, it is not known if the diagnostic performance of MAC varies according to patient demographics that are known to influence peak growth hormone release induced by other secretagogues. Objective: To determine whether the performance of the MAC diagnostic test is affected by age, baseline body mass index (BMI), and sex. Methods: This post hoc analysis included data from a previously published phase 3 study of subjects with a high likelihood of GHD (Group A, considered to have AGHD based on having a low IGF-I level plus either of these: at least 3 other pituitary hormone deficiencies or a structural hypothalamic or pituitary lesion) vs healthy controls (Group D).1 The probability of AGHD was estimated using 4 logistic models fitted to the data: unadjusted, age-adjusted, baseline BMI-adjusted, and sex-adjusted. Each model considers all subjects as independent observations, not taking matching into account. The area under the curve (AUC) of the estimated receiver operating characteristic (ROC) curve (0 to 1 range, where 1 is perfect) from each adjusted model was compared with the AUC from the unadjusted model. The estimated sensitivity and specificity for each model at cutpoint values of 2.8 and 5.1 ng/mL were calculated. Results: Of the 70 subjects included in the analysis, 41 had a high likelihood of GHD and 29 were healthy controls; mean±SD (range) age was 41.7±13.9 (18-66) years, mean±SD (range) BMI was 27.1±4.0 (20.8-36.6) kg/m2, and 56% were male. The ROC AUC for the unadjusted model was 0.9924 (95% CI: 0.9807, 1), age-adjusted ROC AUC was 0.9924 (95% CI: 0.9807, 1), BMI-adjusted ROC AUC was 0.9916 (95% CI: 0.9786, 1), and sex-adjusted ROC AUC was 0.9950 (95% CI: 0.9861, 1). For the unadjusted model at cutpoint values of 2.8 and 5.1, estimated sensitivity was 88% and 93%, and specificity was 97% and 97%. These values remained the same for cutpoint 2.8 when adjusting for age and adjusting for mean or median BMI. At cutpoint 5.1, the values remained the same when adjusting for age and mean BMI. When adjusting for sex, sensitivity for females was 88% and specificity was 93% at cutpoint 2.8, and sensitivity for females was 94% and specificity was 93% at cutpoint 5.1. Sensitivity for males was 88% and specificity was 100% at cutpoint 2.8, and sensitivity for males was 92% and specificity was 100% at cutpoint 5.1. Conclusions: Results of this post hoc analysis show that the diagnostic performance of MAC was not meaningfully affected by age, baseline BMI, or sex over the ranges that were studied. Reference: 1. Garcia JM, et al. J Clin Endocrinol Metab. 2018;103(8):3083-3093.

SUN-431 Primary CNS Lymphoma Involving the Hypothalamus and Pituitary Gland in an Immunocompetent Host Causing Panhypopituitarism

Background: Primary isolated hypothalamic CNS lymphomas in immunocompetent hosts are rare, and the associated presentation of multiple anterior pituitary deficiencies and central diabetes insipidus has been described in 4 cases. Case Report: A 70-year-old man presented with several weeks of progressively worsening fatigue, nausea, vomiting and lethargy. Thyroid function tests obtained by his primary care provider were notable for a TSH 0.14 mU/L (0.35-4.94 mU/L) and free T3 3.4 (4.0-12.8 pg/mL). These abnormal results prompted a brain MRI to be obtained, which revealed a homogenously enhancing mass in the hypothalamus extending bilaterally, 24 x 18 x 16 mm in size. The patients was hospitalized for worsening symptoms and hypotension; left upper lid ptosis was noted on examination, as well. Laboratory tests were notable for a Na+ 139 mmol/L (136-144 mmol/L), K+ 4.0 mmol/L (3.5-5.0 mmol/L), glucose 80 mg/dL (64-128 mg/dl), cortisol 2.4 (0.0-9.0 ug/dL at 2000 hrs), ACTH 5 pg/mL (7-69 pg/mL), TSH 0.56 mU/L (0.35-4.94 mU/L), Free T4 0.5 ng/dL (0.8-1.7 ng/dL), FSH 0.7 IU/L (1.5-12.4 IU/L), LH 0.1 IU/L (1.7-8.6 IU/L), GH 0.73 ng/mL (0.05-3.0 ng/mL), IGF-1 61 ng/mL (27-246 ng/mL) and ACE level 51 U/L (9-67 U/L). HIV and Hepatitis B serology were both negative. He was treated with hydrocortisone 50 mg q8h with rapid improvement in blood pressure and symptoms. He underwent endoscopic brain biopsy with pathologic examination indicating B cell lymphoma was present. There was insufficient tissue sample for flow cytometry. PET/CT was negative for other hyper-metabolic lesions. Subsequent bone marrow biopsy showed normal marrow with trilineage hematopoiesis; there was no morphological or flow cytometric evidence of hematological or distant malignancy including lymphoma. He was discharged from the hospital with hydrocortisone 20 mg in the morning and 10 mg in the afternoon, Levothyroxine 88 mcg daily, and desmopressin 50 mcg inhaled daily. He received treatment with high-dose methotrexate, rituximab and temozolomide. Brain MRI after 2 cycles of chemotherapy showed complete resolution of the mass. The ptosis of the left eye remained unchanged, and the patient remains on hydrocortisone, levothyroxine and desmopressin. Conclusion: Although primary CNS lymphomas are rare in immunocompetent persons, and are particularly rare when presenting in the hypothalamus and pituitary gland, they should be considered in persons presenting with concurrent anterior and posterior pituitary deficiencies. Other important differential diagnoses of simultaneous anterior and posterior pituitary deficiencies with simultaneous hypothalamic and pituitary lesions include malignancies such as craniopharyngioma, metastatic melanoma, renal cell carcinoma and germ cell tumors; and infiltrative diseases such as sarcoidosis, IgG4-related hypophysitis, amyloidosis, and hemochromatosis.

Posterior hypothalamus-sparing surgery improves outcome after childhood craniopharyngioma.

ObjectiveQuality of life (QoL) is frequently impaired in childhood-onset craniopharyngioma (CP) by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or surgical hypothalamic lesions (HL) determine outcome, is controversial.DesignSurvival and outcome of CPs recruited between 2007 and 2014 in KRANIOPHARYNGEOM 2007 were analyzed with regard to reference-confirmed presurgical HI and surgical HL.MethodsRadiological findings, BMI and QoL were assessed at diagnosis and during follow-up. QoL was assessed using Pediatric Quality of Life (PEDQOL) questionnaire.ResultsOne hundred sixty-nine CPs were included presenting with no HI (n = 11), anterior (n = 49) and anterior + posterior (a + p) HI (n = 109) prior to surgery. The latter 109 were analyzed for postoperative HL (no lesion: n = 23, anterior HL: n = 29, a + pHL: n = 57). Progression-free survival (PFS) was higher after complete resection. The highest PFS was observed in CP with a + pHL, especially when compared between non-irradiated subgroups (P = 0.006). Overall survival (OS) rates were 1.0 in all subgroups. CP with a + pHL developed higher BMI (P ≤ 0.001) during follow-up compared between subgroups. 55/109 pts with a + pHI completed PEDQOL at diagnosis (48/109 at 3 years follow-up). QoL was worse for a + pHL patients in terms of physical, social and emotional functionality when compared with the anterior HL and no HL subgroup. BMI development and QoL during follow-up were similar for patients with anterior HL and without HL.ConclusionsPosterior hypothalamus-sparing surgical strategies are associated with higher QoL, decreased development of obesity and lower PFS in CP.

Brain MRI Findings in Pediatric-Onset Neuromyelitis Optica Spectrum Disorder: Challenges in Differentiation from Acute Disseminated Encephalomyelitis.

Differentiating pediatric-onset neuromyelitis optica spectrum disorder from acute disseminated encephalomyelitis could be challenging, especially in cases presenting with only brain manifestations. Our purpose was to investigate brain MR imaging features that may help distinguish these 2 entities. We retrospectively examined initial brain MR imaging studies of 10 patients with pediatric-onset neuromyelitis optica spectrum disorder (female/male ratio, 7:3) and 10 patients with acute disseminated encephalomyelitis (female/male ratio, 2:8). The mean age of the patients was 10.3 ± 5.6 and 8.7 ± 5.3 years, respectively. Brain lesions were evaluated with respect to location, extent, expansion, T1 hypointensity, contrast enhancement/pattern, and diffusion characteristics. The χ2 test (Yates or Fisher exact χ2tests) was used to compare differences between groups. Cerebral subcortical ± juxtacortical and pons ± middle cerebellar peduncle were the most frequent locations involved in both neuromyelitis optica spectrum disorder (n = 5 and 4, respectively) and acute disseminated encephalomyelitis (n = 9 and 7, respectively). Thalamic lesions were more frequent in acute disseminated encephalomyelitis (P = .020) and were detected only in 1 patient with neuromyelitis optica spectrum disorder. None of the patients with neuromyelitis optica spectrum disorder had hypothalamic, internal capsule, or cortical lesions. The internal capsule involvement was found to be significantly different between groups (P = .033). There was no significant difference in terms of extent, expansion, T1 hypointensity, contrast enhancement/pattern, and diffusion characteristics. Although there is a considerable overlap in brain MR imaging findings, thalamic and internal capsule involvement could be used to differentiate pediatric-onset neuromyelitis optica spectrum disorder from acute disseminated encephalomyelitis.

The Pathology of Hyperthyroidism.

This article reviews those pathologic lesions which are associated with clinical and/or biochemical hyperthyroidism. Beginning with the descriptive pathology of classical Graves' disease and the less common toxic nodular goiter and hyper-functioning thyroid nodules, this paper describes the effects of non-thyroidal hormones, glandular function (including pituitary and hypothalamic lesions), ectopic production of thyroid stimulating proteins by non-thyroidal neoplasms, exogenous drug reactions causing hyper-function and finally conditions associated with a mechanic- destructive cause of hyperthyroidism.

High prevalence of syndromic disorders in patients with non-isolated central precocious puberty.

Objective Non-idiopathic CPP is caused by acquired or congenital hypothalamic lesions visible on MRI or is associated with various complex genetic and/or syndromic disorders. This study investigated the different types and prevalence of non-isolated CPP phenotypes. Design and Methods This observational cohort study included all patients identified as having non-idiopathic CPP in the database of a single academic pediatric care center over a period of 11.5 years. Patients were classified on the basis of MRI findings for the CNS as having either hypothalamic lesions or complex syndromic phenotypes without structural lesions of the hypothalamus. Results In total, 63 consecutive children (42 girls and 21 boys) with non-isolated CPP were identified. Diverse diseases were detected, and the hypothalamic lesions visible on MRI (n = 28, 45% of cases) included hamartomas (n = 17; either isolated or with an associated syndromic phenotype), optic gliomas (n = 8; with or without neurofibromatosis type 1), malformations (n = 3) with interhypothalamic adhesions (n = 2; isolated or associated with syndromic CNS midline abnormalities, such as optic nerve hypoplasia, ectopic posterior pituitary) or arachnoid cysts (n = 1). The patients with non-structural hypothalamic lesions (n = 35, 55% of cases) had narcolepsy (n = 9), RASopathies (n = 4), encephalopathy or autism spectrum disorders with or without chromosomal abnormalities (n = 15) and other complex syndromic disorders (n = 7). Conclusion Our findings suggest that a large proportion (55%) of patients with non-isolated probable non-idiopathic CPP may have complex disorders without structural hypothalamic lesions on MRI. Future studies should explore the pathophysiological relevance of the mechanisms underlying CPP in these disorders.

Hypodipsic-hypernatremia syndrome in an adult with polycythemia: a case report

BackgroundHypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule.Case presentationA 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151 mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia.ConclusionHypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

Periostin concentrations in childhood-onset craniopharyngioma patients.

Periostin is highly expressed in craniopharyngioma (CP)-associated fibroblasts and has been identified as a marker for non-alcoholic fatty liver disease (NAFLD). Half of CP patients with hypothalamic syndrome develop NAFLD. We hypothesized that periostin concentration is elevated in biological fluids of CP and associated with pathological hepatic parameters, indicating increased risk for NAFLD. A cross-sectional study on 35 patients with sellar masses (SMP) recruited in the German Childhood Craniopharyngioma Registry (32 CP, 2 xanthogranuloma, 1 pilocytic astrocytoma), three short-statured patients with isolated growth hormone deficiency, five short-statured patients with normal findings in GH-stimulating tests and decreased insulin-like growth factor (IGF)-1 and seven healthy controls. Periostin was measured by Elisa in serum, urine and saliva. Periostin serum, urine and saliva concentrations in CP were similar to concentrations of the other groups. Hypothalamic involvement/hypothalamic lesions, degree of obesity as well as hepatic enzymes were not associated with elevated periostin concentrations. Due to low patient numbers with pathological hepatic parameters, missing imaging data on the degree of steatosis hepatis and the lack of histological proof of NAFLD, no definitive conclusions can be drawn from measured periostin concentrations in serum. Interestingly, the subgroup of patients with decreased IGF-1 levels showed elevated concentrations of serum periostin when compared with other groups. In CP, periostin concentrations are not associated with known risk factors for NAFLD such as hepatic and metabolic parameters, obesity and hypothalamic lesions. Accordingly, periostin does not seem to be a suitable marker for NAFLD in CP.

Multiple Bilateral Infarction Involving Bilateral Hypothalamic Lesion Presented with High Fever, Unstable Blood Pressure

Multiple Bilateral Infarction Involving Bilateral Hypothalamic Lesion Presented with High Fever, Unstable Blood Pressure

Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis

Background: Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. Objective: To describe a cohort of patients with MS, who developed EH. Methods: Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. Results: Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). Conclusion: EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

ContextPatients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown.ObjectiveTo determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP.DesignA cross-sectional study with a median follow-up time of 22 (6–49) years after operation.SettingThe South Medical Region of Sweden (2.5 million inhabitants).ParticipantsIncluded were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958–2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients.Main outcome measuresSubjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry.ResultsRight uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26–38% of the variation, and with visuospatial ability and executive function, explaining 19–29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory.ConclusionsA structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

Hypothalamic and pituitary stalk lesions in adolescents

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats.

In the past, we showed that large electrolytic lesions of the dorsomedial hypothalamus (DMH) promoted hypothermia in cold-exposed restrained rats, but attenuated hypothermia in rats challenged with a high dose of bacterial lipopolysaccharide (LPS) in a thermogradient apparatus. The goal of this study was to identify the thermoeffector mechanisms and DMH representation of the two phenomena and thus to understand how the same lesion could produce two opposite effects on body temperature. We found that the permissive effect of large electrolytic DMH lesions on cold-induced hypothermia was due to suppressed thermogenesis. DMH-lesioned rats also could not develop fever autonomically: they did not increase thermogenesis in response to a low, pyrogenic dose of LPS (10 μg/kg, i.v.). In contrast, changes in thermogenesis were uninvolved in the attenuation of the hypothermic response to a high, shock-inducing dose of LPS (5000 μg/kg, i.v.); this attenuation was due to a blockade of cold-seeking behavior. To compile DMH maps for the autonomic cold defense and for the cold-seeking response to LPS, we studied rats with small thermal lesions in different parts of the DMH. Cold thermogenesis had the highest representation in the dorsal hypothalamic area. Cold seeking was represented by a site at the ventral border of the dorsomedial nucleus. Because LPS causes both fever and hypothermia, we originally thought that the DMH contained a single thermoregulatory site that worked as a fever–hypothermia switch. Instead, we have found two separate sites: one that drives thermogenesis and the other, previously unknown, that drives inflammation-associated cold seeking.SIGNIFICANCE STATEMENT Cold-seeking behavior is a life-saving response that occurs in severe systemic inflammation. We studied this behavior in rats with lesions in the dorsomedial hypothalamus (DMH) challenged with a shock-inducing dose of bacterial endotoxin. We built functional maps of the DMH and found the strongest representation of cold-seeking behavior at the ventral border of the dorsomedial nucleus. We also built maps for cold-induced thermogenesis in unanesthetized rats and found the dorsal hypothalamic area to be its main representation site. Our work identifies the neural substrate of cold-seeking behavior in systemic inflammation and expands the functional topography of the DMH, a structure that modulates autonomic, endocrine, and behavioral responses and is a potential therapeutic target in anxiety and panic disorders.

Hypothalamic hamartoma: Epileptogenesis beyond the lesion?

The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step.

Gene Expression Analysis in Rat Pancreas Observed with Whole-Transcript Exon Array after Ventromedial Hypothalamic Lesions

Background: It was reported previously that using Affymetrix Rat Genome 230 2.0, one of a class of standard 3′ based arrays, ventromedial hypothalamic (VMH) lesions affected the expressions of cell proliferation-related genes, neuron-related genes, and metabolism-related genes. The released Affymetrix Rat Gene 1.0 ST array has 2 major differences compared with standard 3′ based arrays, including Rat Genome 230 2.0: it interrogates the entire mRNA transcript and uses DNA targets. Purpose: This study is aimed at assessing the impact of these differences on the array performance. Methods: The study used Rat Gene 1.0 ST array, one of a class of whole-transcript rat exon arrays to examine the cellular mechanisms of gene regulation in the rat pancreas after VMH lesions. Results: Although the results showed that VMH lesions regulated genes involved in enzymes, metabolism, transport, binding differentiation, migration, morphology, apoptosis, neuron and immunity, the probes identified by these 2 arrays were remarkably different. Conclusion: This study also confirmed that VMH lesions may affect the expression of many functional genes in rat pancreas.

Anorexia-cachexia syndrome-like hypothalamic neuroendocrine dysfunction in a patient with a papillary craniopharyngioma.

The craniopharyngiomas are solid cystic suprasellar tumors that can present extension to adjacent structures, conditioning pituitary and hypothalamic dysfunction. Within hypothalamic neuroendocrine dysfunction, we can find obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, imbalances in the regulation of body temperature, thirst, heart rate and/or blood pressure and alterations in dietary intake (like anorexia). We present a rare case of anorexia–cachexia syndrome like a manifestation of neuroendocrine dysfunction in a patient with a papillary craniopharyngioma. Anorexia–cachexia syndrome is a complex metabolic process associated with underlying illness and characterized by loss of muscle with or without loss of fat mass and can occur in a number of diseases like cancer neoplasm, non-cancer neoplasm, chronic disease or immunodeficiency states like HIV/AIDS. The role of cytokines and anorexigenic and orexigenic peptides are important in the etiology. The anorexia–cachexia syndrome is a clinical entity rarely described in the literature and it leads to important function limitation, comorbidities and worsening prognosis.Learning points:Suprasellar lesions can result in pituitary and hypothalamic dysfunction.The hypothalamic neuroendocrine dysfunction is commonly related with obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, but rarely with anorexia–cachexia.Anorexia–cachexia syndrome is a metabolic process associated with loss of muscle, with or without loss of fat mass, in a patient with neoplasm, chronic disease or immunodeficiency states.Anorexia–cachexia syndrome results in important function limitation, comorbidities that influence negatively on treatment, progressive clinical deterioration and bad prognosis that can lead the patient to death.Anorexia–cachexia syndrome should be suspected in patients with emaciation and hypothalamic lesions.

Syndrome of inappropriate antidiuretic hormone accompanied by bilateral hypothalamic and anterior thalamic lesions with serum antiaquaporin 4 antibody

We described a rare case of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and severe unconsciousness accompanied by bilateral hypothalamic and anterior thalamic lesions with positive serum antiaquaporin 4...

Adult Neurogenesis in Injury-Induced Self-Repair: Use It or Lose It.

One of the most hotly pursued topics in neuroscience and therapeutic medicine is the use of stem cells in the adult brain. Growing in parallel to this emerging field is the recognition that the adult brain is indeed capable of generating new cells. While neurogenesis was understood to be restricted to a few areas, recent studies suggest that damage to the adult brain can trigger neurogenesis even in regions outside of these specific areas. This finding raises the possibility that neurons born in response to perturbation in the brain may be involved in the recovery of function in the damaged adult brain. The key is understanding how to cultivate these newborn cells, because they do not remain viable if they are not accepted into the damaged network of interconnected neurons which support specific functions. From a birth site, undifferentiated precursor cells or neurons undergo migration and differentiation. Many factors influence the safe journey of migrating cells and their survival after maturation at their destination.This review will present evidence from ring dove studies that an activity-dependent mechanism underlies the survival of adult newborn neurons and establishment of their functionality. This evidence includes: [1] unique electrophysiological properties or specific connectivity associated with various type of neurons involved in ring dove coo behavior and reproductive function, [2] emergence of electrophysiological properties and specific projection neurons emanating from newborn neurons after hypothalamic lesion, and finally [3] collective behavioral analyses of social stimulations suggesting that sensorimotor events contribute to the integration of new neurons and reinstatement of function.