Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation

PURPOSE: With the advent of intensity-modulated radiotherapy, the ability to limit the radiation dose to normal tissue offers an avenue to limit side effects. This study attempted to delineate the distribution of brain metastases with relation to the hippocampus for the purpose of exploring the viability of tomotherapy-guided hippocampal sparing therapy potentially to reduce neurocognitive deficits from radiation. METHODS AND MATERIALS: The pre-radiotherapy T1-weighted, postcontrast axial MR images of 100 patients who received whole brain radiotherapy, stereotactic radiosurgery, or a radiosurgical boost following whole brain radiotherapy between 2002 and 2006 were examined. We contoured brain metastases as well as hippocampi with 5-, 10-, and 15-mm expansion envelopes. RESULTS: Of the 272 identified metastases, 3.3% (n = 9) were within 5 mm of the hippocampus, and 86.4% of metastases were greater than 15 mm from the hippocampus (n = 235). The most common location for metastatic disease was the frontal lobe (31.6%, n = 86). This was followed by the cerebellum (24.3%, n = 66), parietal lobe (16.9%, n = 46), temporal lobe (12.9%, n = 35), occipital lobe (7.7%, n = 21), deep brain nuclei (4.0%, n = 11), and brainstem (2.6%, n = 7). CONCLUSIONS: Of the 100 patients, 8 had metastases within 5 mm of the hippocampus. Hence, a 5-mm margin around the hippocampus for conformal avoidance whole brain radiotherapy represents an acceptable risk, especially because these patients in the absence of any other intracranial disease could be salvaged using stereotactic radiosurgery. Moreover, we developed a hippocampal sparing tomotherapy plan as proof of principle to verify the feasibility of this therapy in the setting of brain metastases.     

Arachnoid cyst with GnRH-dependent sexual precocity and growth hormone deficiency

The coexistence of gonadotropin-releasing hormone (GnRH)-dependent sexual precocity and growth hormone deficiency in patients with arachnoid cysts is rarely reported, and its pathogenesis is not well recognized. This report describes an 11-year-old female who had a huge intracranial arachnoid cyst with initial symptoms and signs of sexual precocity. Her brain magnetic resonance imaging revealed distorted hypothalamus with a thin and stretched pituitary stalk. After treatment with cysto-peritoneal shunting and gonadotropin-releasing hormone analogue, her puberty was arrested and subnormal growth rate was observed. Catch-up growth was detected after growth hormone therapy. Hence, coexistence of gonadotropin-releasing hormone-dependent sexual precocity and growth hormone deficiency in this patient was confirmed.     

Periodic lateralized epileptiform discharges of pediatric patients in Taiwan

Periodic lateralized epileptiform discharges are special electroencephalographic abnormalities present in adults with stroke, brain tumor, intracranial hemorrhage, or other rare etiologies. Few reports focused on the etiologies in pediatric patients. We retrospectively reviewed 8002 of our pediatric electroencephalographic records for the past 12 years and listed all associated illness and their outcomes. Forty-four children with periodic lateralized epileptiform discharges were collected. We found that there was an obvious difference in etiologies of our pediatric patients from those reported in the literature. Nearly two thirds of our patients (28 children) were associated with central nervous system infections. The other etiologies included head injury, encephalopathy, epilepsy, and others. Herpes simplex virus was responsible for two thirds (12) of the 18 children with identified pathogens causing a central nervous system infection. Ten patients failed to have a defined pathogen. Periodic lateralized epileptiform discharges have a different clinical significance in pediatric patients than in adults. In Taiwan, central nervous system infection is the most common etiology of periodic lateralized epileptiform discharges in pediatric patients. Herpes simplex virus, although the most common pathogen, should not be considered to be the only cause of encephalitis in children with periodic lateralized epileptiform discharges.     

Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention

Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone protein and is overexpressed in various cancers. However, it is unclear how significance of this molecule play an active role contributing to the oncogenic effect of head and neck cancer (HNC). To investigate the potential function of Grp78, six HNC cell lines were used. We found that Grp78 is highly expressed in all six cell lines and many of the proteins were localized in the periphery regions, implying other function of this molecule aside from endoplasmic reticulum stress response. Knockdown of Grp78 by small interfering RNA significantly reduced cell growth and colony formation to 53% to 12% compared with that of controls in all six HNC cell lines. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 23% to 2% in all these cell lines tested. In vivo xenograft studies showed that administration of Grp78-small interfering RNA plasmid into HNC xenografts significantly inhibited both tumor growth in situ (>60% inhibition at day 34) and liver metastasis (>90% inhibition at day 20). Our study showed that Grp78 actively regulates multiple malignant phenotypes, including cell growth, migration, and invasion. Because knockdown Grp78 expression succeeds in the reduction of tumor growth and metastatic potential, this molecule may serve as a molecular target of therapeutic intervention for HNC. [Mol Cancer Ther 2008;7(9):2788-97].     

Traumatic hyoid bone fracture in patient wearing a helmet: a case report

Fractures of hyoid bone are rare and most of the injuries cause by strangulation. Hyoid bone fractures are usually the result of direct trauma to the neck through manual strangulation or hanging, blunt trauma or from projectiles. But hyoid bone fracture caused by helmet strap has not been reported before. We present a young man wearing a helmet had an isolated hyoid bone fractures after a motorcycle-to-motorcycle accident. So, we should be more aware that helmet wearing riders are prone to have this kind of injury.     

Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running

Physical exercise is known to promote adult neurogenesis, although the underlying mechanisms remain unclear. Glucocorticoid (corticosterone in rodents) is a factor that is known to affect neurogenesis. As physical exercise modulates corticosterone secretion, we hypothesized that corticosterone signaling is involved in exercise-induced adult neurogenesis. We chose treadmill running (TR) to accurately define the intensity and duration of exercise. Our results showed that 5 weeks of TR increased the doublecortin (DCX)-positive neuronal progenitor cells (NPCs) in adult hippocampus and transiently increased the serum corticosterone level at the end of the TR protocol. This protocol reduced the levels of hippocampal mineralocorticoid receptor (MR); however, glucocorticoid receptor levels were unaltered. We then investigated whether reducing corticosterone levels by bilateral adrenalectomy (ADX) attenuated the TR-enhanced adult neurogenesis. Our results showed that ADX not only blocked the TR-induced downregulation of MR, but also reduced the number of TR-enhanced NPCs. In order to examine the role of MR downregulation in TR-induced adult neurogenesis, animals were treated repeatedly with a selective MR antagonist, spironolactone, for 3 weeks. The results revealed that spironolactone increased the number of spontaneously occurring and TR-induced NPC in the dentate area. Further analysis revealed that spironolactone treatment did not alter precursor cell proliferation, but increased the number of DCX-positive NPCs, suggesting that blockage of MR signaling either facilitates the differentiation of progenitor cells towards neurons and/or enhances the survival of NPCs. Taken together, the data indicated that induction of NPCs in the dentate area of adult hippocampus by TR is partly due to the downregulation of glucocorticoid/MR signaling, which subsequently enhances differentiation along a neuronal lineage and/or NPC survival.     

Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1

Objectives –  To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients.
Materials and methods –  Seventeen patients with classic DM1 were administered intelligence and neuropsychological tests and brain MRI focusing on a semi-quantitative rating scale of subcortical white matter lesions (WMLs). Statistical analysis was measured to evaluate the correlation among clinical manifestations, intelligence, brain MRI abnormalities, and CTG repeat expansion.
Results –  There were statistically significant correlations between intelligence test and insular WMLs for all DM1 patients and between intelligence quotient and temporal WMLs for those patients with less than 400 of the CTG repeat size. We also documented that temporal WMLs were related to the disease course, and frontal WMLs were correlated with aging in all DM1 patients. However, a poor correlation was found among CTG repeat size and clinical pictures, neuropsychological impairments, and brain MRI abnormalities in all DM1 patients.
Conclusion –  These results suggest that subcortical WMLs are correlated with focal dementia in classic DM1 patients. Temporal and insular WMLs may be responsible for the global intellectual dysfunction of adult DM1 patients.