Increased Daytime Sleepiness in Patients with Childhood Craniopharyngioma and Hypothalamic Tumor Involvement: Review of the Literature and Perspectives

Childhood craniopharyngiomas are rare embryogenic malformations of the sellar region, presumably derived from Rathke cleft epithelium. The overall survival rates after neurosurgical intervention and/or irradiation are high (92%). However, the quality of survival is frequently impaired due to endocrine deficiencies, sleep disturbances, daytime sleepiness, and severe obesity caused by hypothalamic lesions. Based on self-assessment using nutritional diaries, caloric intake was similar in patients and BMI-matched controls. Analyses of physical activity by accelerometric measurements showed a markedly lower level of physical activity. Significant daytime sleepiness and disturbances of circadian rhythms have been demonstrated in obese childhood craniopharyngioma patients. Daytime sleepiness and obesity in these patients were both correlated with low nocturnal and early morning melatonin levels. Polysomnographic studies in patients with severe daytime sleepiness revealed sleeping patterns typical for secondary narcolepsy. Reports on a beneficial effect of treatment with central stimulating agents supported the hypothesis that secondary narcolepsy should be considered as a rare cause for severe daytime sleepiness in patients with childhood craniopharyngioma

Diagnostics, Treatment, and Follow-Up in Craniopharyngioma

Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and parasellar region, with up to half the 0.5–2.0 new cases per million population per year occur in children and adolescents. Diagnosis profile for pediatric and adult craniopharyngioma is characterized by a combination of headache, visual impairment, and polyuria/polydipsia, which can also include significant weight gain. In children, growth retardation, and/or premature puberty often occur later or postoperatively. Recommended therapy with favorable tumor localization is complete resection; with unfavorable tumor localization (optic nerve and/or hypothalamic involvement), consensus is still pending whether a limited resection followed by local irradiation is more prudent. Even though overall survival rates are high (92%), recurrences after complete resection and progressions after incomplete resection can be expected. Accordingly, a randomized multinational trial (KRANIOPHARYNGEOM 2007) has been established to identify optimal diagnosis, treatment (particularly the ideal time point of irradiation after incomplete resection), and quality of life strategies of this chronic disease – most notably the morbid hypothalamic obesity in ∼50% of long-term survivors. We report on craniopharyngioma origins, its pathological manifestations, and specific challenges these sequelae pose regarding diagnosis, treatment, and life-long multi-discipline quality of life management for both adult and childhood craniopharyngioma patients

RARE-01: Cerebral infarction in childhood-onset craniopharyngioma patients: results of KRANIOPHARYNGEOM 2007 [Abstract]

BACKGROUND: Cerebral infarction (CI) is a known vascular complication following treatment of suprasellar tumors. Risk factors for CI, incidence rate, and long-term prognosis are unknown for patients with childhood-onset craniopharyngioma (CP). METHODS: MRI of 244 CP patients, recruited between 2007 and 2019 in KRANIOPHA-RYNGEOM 2007, were reviewed for CI. Risk factors for CI and outcome after CI were analyzed. RESULTS: Twenty-eight of 244 patients (11%) presented with CI based on reference assessment of MRI. One CI occurred before initial surgery and one case of CI occurred after release of intracystic pressure by a cyst catheter. 26 of 28 CI were detected after surgical tumor resection at a median postoperative interval of one day (range: 0.5 - 53 days). Vascular lesions during surgical procedures were documented in 7 cases with CI. No relevant differences with regard to surgical approaches were found. In all 12 irradiated patients, CI occurred before irradiation. Multivariable analyses showed that hydrocephalus and gross-total resection at the time of primary diagnosis / surgery both were risk factors for CI. After CI, quality of life (PEDQOL) and functional capacity (FMH) were impaired. CONCLUSIONS: CI occurs in 11% of surgically-treated CP cases. Degree of resection and increased intracranial pressure are risk factors, which should be considered in the planning of surgical procedures for prevention of CI

Lower-Resolution Retrieval of Scenes in Older Adults With Subjective Cognitive Decline

Objective Scenes with more perceptual detail can help detect subtle memory deficits more than scenes with less detail. Here, we investigated whether older adults with subjective cognitive decline (SCD) show less brain activation and more memory deficits to scenes with more (vs. scenes with less) perceptual detail compared to controls (CON). Method In 37 healthy older adults (SCD: 16), we measured blood oxygenation level-dependent-functional magnetic resonance imaging during encoding and behavioral performance during retrieval. Results During encoding, higher activation to scenes with more (vs. less) perceptual detail in the parahippocampal place area predicted better memory performance in SCD and CON. During retrieval, superior performance for new scenes with more (vs. less) perceptual detail was significantly more pronounced in CON than in SCD. Conclusions Together, these results suggest a present, but attenuated benefit from perceptual detail for memory retrieval in SCD. Memory complaints in SCD might, thus, refer to a decreased availability of perceptual detail of previously encoded stimuli

Nuchal skinfold thickness in pediatric brain tumor patients

BACKGROUND: Severe obesity and tumor relapse/progression have impact on long-term prognosis in pediatric brain tumor patients. METHODS: In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) on magnetic-resonance imaging (MRI) follow-up monitoring as a parameter for assessment of nuchal adipose tissue in 177 brain tumor patients (40 World Health Organization (WHO) grade 1–2 brain tumor; 31 grade 3–4 brain tumor; 106 craniopharyngioma), and 53 healthy controls. Furthermore, body mass index (BMI), waist-to-height ratio, caliper-measured skinfold thickness, and blood pressure were analyzed for association with NST. RESULTS: Craniopharyngioma patients showed higher NST, BMI, waist-to-height ratio, and caliper-measured skinfold thickness when compared to other brain tumors and healthy controls. WHO grade 1–2 brain tumor patients were observed with higher BMI, waist circumference and triceps caliper-measured skinfold thickness when compared to WHO grade 3–4 brain tumor patients. NST correlated with BMI, waist-to-height ratio, and caliper-measured skinfold thickness. NST, BMI and waist-to-height ratio were associated with increased blood pressure. In craniopharyngioma patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased. CONCLUSIONS: NST could serve as a novel useful marker for regional nuchal adipose tissue. NST is highly associated with body mass and waist-to-height ratio, and easily measurable in routine MRI monitoring of brain tumor patients

Cerebral infarction in childhood-onset craniopharyngioma patients: results of KRANIOPHARYNGEOM 2007

BACKGROUND: Cerebral infarction (CI) is a known vascular complication following treatment of suprasellar tumors. Risk factors for CI, incidence rate, and long-term prognosis are unknown for patients with childhood-onset craniopharyngioma (CP). METHODS: MRI of 244 CP patients, recruited between 2007 and 2019 in KRANIOPHARYNGEOM 2007, were reviewed for CI. Risk factors for CI and outcome after CI were analyzed. RESULTS: Twenty-eight of 244 patients (11%) presented with CI based on reference assessment of MRI. One CI occurred before initial surgery and one case of CI occurred after release of intracystic pressure by a cyst catheter. 26 of 28 CI were detected after surgical tumor resection at a median postoperative interval of one day (range: 0.5-53 days). Vascular lesions during surgical procedures were documented in 7 cases with CI. No relevant differences with regard to surgical approaches were found. In all 12 irradiated patients, CI occurred before irradiation. Multivariable analyses showed that hydrocephalus and gross-total resection at the time of primary diagnosis/surgery both were risk factors for CI. After CI, quality of life (PEDQOL) and functional capacity (FMH) were impaired. CONCLUSIONS: CI occurs in 11% of surgically-treated CP cases. Degree of resection and increased intracranial pressure are risk factors, which should be considered in the planning of surgical procedures for prevention of CI

Predictive coding in ASD: inflexible weighting of prediction errors when switching from stable to volatile environments

Individuals with autism spectrum disorder (ASD) have been widely reported to show atypicalities in predictive coding, though there remains a controversy regarding what causes such atypical processing. Suggestions range from overestimation of volatility to rigidity in the reaction to environmental changes. Here, we tested two accounts directly using duration reproduction of volatile and non-volatile interval sequences. Critically, both sequences had the same set of intervals but differed in their stimulus presentation orders. Comparing individuals with ASD vs. their matched controls, we found both groups to respond to the volatility in a similar manner, albeit with a generally reduced prior in the ASD group. Interestingly, though, relative to the control group, the ASD group exhibited a markedly reduced trust in the prior in the volatile trial session when this was performed after the non-volatile session, while both groups performed comparably in the reverse session order. Our findings suggest that it is not the learning of environmental volatility that is compromised in ASD. Rather, it is their response to a change of the volatility regimen from stable to volatile, which causes a highly inflexible weighting of prediction errors.Competing Interest StatementThe authors have declared no competing interest

Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network whereas amygdala nuclei as parts of the salience network, with both networks forming collectively a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. From the resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: Ns = 101, 61, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems were characterized by a consistent involvement of amygdala, hippocampus, and entorhinal cortex, but a variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connected to salience, thalamic-brainstem, and default mode networks – the major cortical and subcortical parts of the allostatic-interoceptive system. These results provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system

Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system.

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala nuclei as parts of the salience network, with both networks collectively forming a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. Capitalizing on resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: N ​= ​101, 60, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level, MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems are characterized by consistent involvement of amygdala, hippocampus, and entorhinal cortex, but variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connect to salience, thalamic-brainstem, and default mode networks – the major cortical and subcortical components of the allostatic-interoceptive system. These findings provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system