Severe chronic nonlichenoid oral mucositis in pembrolizumab-treated patients: new cases and a review of the literature.

Aim: To report of severe chronic oral mucositis (OM) in two pembrolizumab-treated cancer patients. Materials & methods: A retrospective chart review was performed. Inclusion/exclusion criteria detected patients that developed OM during pembrolizumab immunotherapy. In addition, we searched the literature for nonlichenoid OM in immunotherapy-treated cancer patients. Results: Two male patients treated for anaplastic astrocytoma and lung adenocarcinoma were included. Extensive painful OM (grade 4) developed in both patients during the course of immunotherapy and the ulcerations remained >30 weeks (>16 weeks after stopping immunotherapy). Superficial mucocele appeared in one patient. In one patient, pain relief was achieved with photobiomodulation (low-level laser) therapy. Conclusion: OM induced by immunotherapy may be a major cause of suffering and eating difficulties. In most cases, the OM lasted for months even after the drug was stopped. There is a controversy regarding the beneficial effect of corticosteroids on OM in these patients.

Effect of cognitive rehabilitation in a case of thalamic astrocytoma.

We describe the effectiveness of rehabilitative training for a neuropsychological deficit following the removal and treatment of a fibrillary astrocytoma (Grade II) in a young man. The rehabilitative training was based on cognitive and motivational techniques and has been carried out for a period of 3 months (2 times per week). The results, even if limited to a single case, seem to support the idea that cognitive rehabilitation should facilitate the brain's reorganization of basic cognitive functions in the neuro-oncologic field.

Neuropsychological Deterioration Predicts Tumor Progression in a Young Boy With Bithalamic Glioma.

A description is given of the clinical, neuropsychological, and neuroimaging evolution of a 12-year-old boy (CG) who presented with bilateral thalamic astrocytoma (World Health Organization Grade 2). CG underwent an extensive neuropsychological assessment immediately after biopsy prior to any medical therapies and was followed up for 3 years until death. Neuropsychological functioning was thoroughly investigated by means of a detailed battery that included intelligence and cognitive functions. Evolution was characterized by cognitive deterioration that preceded neuroimaging signs of tumor progression. Starting from normal cognitive organization, the child exhibited visuospatial memory deficits and, afterward, diffuse cognitive impairment. The role of neuropsychological assessment in detecting early disease progression is discussed, mainly for rare pathologies whose evolution may be extremely variable.

Pilocytic astrocytoma with anaplastic features presenting good long-term clinical course after surgery alone: a case report.

PURPOSE: Pilocytic astrocytomas (PAs) are the most common brain tumor in children and typically have an excellent prognosis. However, some PAs show histologically anaplastic features. It is reported that PAs with anaplastic features often need the postoperative radiation and chemotherapy due to aggressiveness such as early local recurrence and dissemination. We describe an interesting case of primary anaplastic PA with good clinical course in the long-term. METHODS: A 10-year-old man presented with worsening headache and vomiting. Magnetic resonance imaging (MRI) showed a large cystic tumor with contrast-enhanced solid component in a right occipital lobe. Magnetic resonance spectroscopy (MRS) showed the decrease of N-acetylaspartate (NAA) and the increase of choline and lipids, which suggested the malignancy. RESULTS: The patient was operated with an occipital lobectomy. The tumor was incompletely resected due to the deep invasion to the inner wall of lateral ventricle. Pathological diagnosis was a pilocystic astrocytoma with anaplastic features. Although aggressive features were suspected from magnetic resonance spectroscopy and pathological findings, the remnant tumor showed no recurrence for 8 years without any postoperative treatments. CONCLUSION: PAs could exhibit variable behavior, and careful managements including wait-and-scan should be considered, because adjuvant therapies may cause child's growth disorder and malignant transformation.

Surgical management of tumors producing the thalamopeduncular syndrome of childhood.

OBJECT: Thalamopeduncular tumors arise at the junction of the inferior thalamus and cerebral peduncle and present with a common clinical syndrome of progressive spastic hemiparesis. Pathologically, these lesions are usually juvenile pilocytic astrocytomas and are best treated with resection with the intent to cure. The goals of this study are to define a common clinical syndrome produced by thalamopeduncular tumors and to discuss imaging characteristics as well as surgical adjuncts, intraoperative nuances, and postoperative complications relating to the resection of these neoplasms. METHODS: The authors present a retrospective review of their experience with 10 children presenting between 3 and 15 years of age with a thalamopeduncular syndrome. Formal preoperative MR imaging was obtained in all patients, and diffusion tensor (DT) imaging was performed in 9 patients. Postoperative MR imaging was obtained to evaluate the extent of tumor resection. A prospective analysis of clinical outcomes was then conducted by the senior author. RESULTS: Pilocytic astrocytoma was the pathological diagnosis in 9 cases, and the other was fibrillary astrocytoma. Seven of 9 pilocytic astrocytomas were completely resected. Radical surgery was avoided in 1 child after DT imaging revealed that the corticospinal tract (CST) coursed through the center of the tumor, consistent with the infiltrative nature of fibrillary astrocytoma as identified by stereotactic biopsy. In 8 patients, tractography served as an important adjunct for designing a surgical approach that spared the CST. In 6 cases the CSTs were pushed anterolaterally, making a transsylvian approach a poor choice, as was evidenced by the first patient in the series, who underwent operation prior to the advent of tractography, and who awoke with a dense contralateral hemiparesis. Thus, subsequent patients with this deviation pattern underwent a transcortical approach via the middle temporal gyrus. One patient exhibited medial deviation of the tracts and another had lateral deviation, facilitating a transtemporal and a transfrontal approach, respectively. CONCLUSIONS: The thalamopeduncular syndrome of progressive spastic hemiparesis presenting in children with or without symptoms of headache should alert the examiner to the possibility of a tumoral involvement of CSTs. Preoperative tractography is a useful adjunct to surgical planning in tumors that displace motor pathways. Gross-total resection of pilocytic astrocytomas usually results in cure, and therefore should be entertained when developing a treatment strategy for thalamopeduncular tumors of childhood.

Guggulipid and nimesulide differentially regulated inflammatory genes mRNA expressions via inhibition of NF-kB and CHOP activation in LPS-stimulated rat astrocytoma cells, C6.

Neuroinflammation is an integral part of neurodegenerative diseases. Lipo-polysacharide (LPS) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of neurological diseases, but its mechanism of action is still not properly known. The effect of guggulipid and nimesulide on LPS-induced neuroinflammatory changes is also not properly understood. This work demonstrated the mechanism of actions of guggulipid and nimesulide on inflammatory genes expressions in LPS-stimulated rat astrocytoma cells, C6. We observed that LPS (10 µg/ml) treatment of rat astrocytoma cells, C6, for 24 h significantly increased intracellular Ca(2+) ion and expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB), C/EBP homologous protein 10 (CHOP), c-fos, and c-jun proteins. At transcriptional stage, LPS upregulated mRNA levels of cyclooxygenase-2 and IL-6 with downregulation in IL-1α, IL-1ß, and microsomal prostaglandin E synthase-1 (mPGES-1) through activating NF-kB translocation. Treatment with guggulipid reversed these LPS-induced changes in rat astrocytoma cells. Treatment with nimesulide also attenuated LPS-induced Ca(2+) ion, iNOS, NF-kB, and c-fos expressions, but does not significantly influence CHOP, c-jun protein expressions, and mRNA levels of IL-6, IL-1α, IL-1ß, and mPGES-1 genes. In conclusion, our findings elucidated the molecular mechanism of neuroinflammation in response to LPS and its modulation by guggulipid and nimesulide in rat astrocytoma cells (C6), which suggest the use of these drugs in the treatment of neuroinflammation-associated disorders.

Stereotactic volumetric resection of thalamic pilocytic astrocytomas.

OBJECTIVE: To describe the surgical approaches, the radiographic and clinical outcomes, and the long-term follow-up of patients harboring thalamic pilocytic astrocytomas after radical resection by means of a stereotactic volumetric technique. METHODS: Seventy-two patients with thalamic pilocytic astrocytomas underwent stereotactic volumetric resection by the senior author (PJK) at the Mayo Clinic between 1984 and 1993 (44 patients) and at New York University Medical Center between 1993 and 2005 (28 patients). Patient demographics, presenting symptoms, surgical approaches, neurological outcomes, pathology, initial postoperative status, and long-term clinical and radiographic follow-up were retrospectively reviewed. RESULTS: On preoperative neurological examinations, 54 of the 72 patients had neurological deficits; of these, 48 had hemiparesis. Postoperative imaging demonstrated gross total resection in 58 patients and minimal (<6 mm) residual tumor in 13 patients. Tumor resection was aborted in one patient. On immediate postoperative examination, 16 patients had significant improvements in hemiparesis. Six patients had worsening of a preexisting hemiparesis and one had a new transient postoperative hemiparesis. There was one postoperative death. After 13 to 20 years of follow-up in the Mayo group (mean, 15 +/- 3 yr) and 1 to 13 years of follow-up in the New York University group (mean, 8 +/- 3 yr), 67 patients were recurrence/progression-free, one had tumor recurrence, and three had progression of residual tumor. There were two shunt-related deaths. On long-term neurological follow-up, 27 patients had significant improvements in hemiparesis; one patient with a postoperative worsening of a preexisting hemiparesis remained unchanged. There were no patients with new long-term motor deficits after stereotactic resection. CONCLUSION: Gross total removal of thalamic pilocytic astrocytomas with low morbidity and mortality can be achieved by computer-assisted stereotactic volumetric resection techniques. Gross total resection of these lesions confers a favorable long-term prognosis without adjuvant chemotherapy and/or radiation therapy and leads to the improvement of neurological deficits.

Bilateral thalamic astrocytoma.

We present a 68-year-old woman who presented with symptoms of frontotemporal dementia. Brain MRI revealed tumor mass in both thalami and according to WHO classification, the tumor corresponded to diffuse fibrillary astrocytoma grade II. This case points to the role of neuroimaging in patients presenting with classical symptoms of dementia.

Disseminated pilocytic astrocytoma involving brain stem and diencephalon: a history of atypical eating disorder and diagnostic delay.

The association of weight loss and pediatric brain tumors that affect the diencephalon or brain stem with weight loss is a recognized, but not fully understood phenomenon. Tumors located in the hypothalamic region may induce the diencephalic syndrome (DS), which is characterized by profound emaciation with almost complete loss of subcutaneous fatty tissue. Tumors that compress or infiltrate the brain stem rarely cause both psychological disturbance and emaciation. The clinical presentation may be different, depending on the location of the lesion and age of the patient. In this report we present an unusual case of severe emaciation in a 4(9)/(12)-year-old girl with a juvenile pilocytic astrocytoma of the hypothalamic region and brain stem with neuroaxis dissemination. This case illustrates the importance of considering intracranial mass-lesions in the differential diagnosis of weight loss, psychological disturbance and atypical eating disorder. We discuss the importance of tumor multifocality and the role of patient age in the clinical presentation with reference to the literature.

[Pilocytic astrocytoma and diencephalic syndrome in an adult with neurofibromatosis type 1].

We report a rare case of pilocytic astrocytoma and diencephalic syndrome occurring together in a 30-year-old woman with neurofibromatosis type 1 (NF-1). Diencephalic syndrome included emaciation and somnolence. Gadolinium-enhanced magnetic resonance imaging revealed a brain tumor in the optic chiasmal-hypothalamic region, which invaded the thalamus, brain stem and cerebellum. A biopsy specimen from the chiasmal tumor was compatible with pilocytic astrocytoma. Although she received radiation therapy, she died 22 months after the onset of the disease.

Environmental tilt illusion as the only symptom of a thalamic astrocytoma.

A 14-year-old girl experienced two episodes of environmental tilt illusion. During both episodes, which lasted less than 1 minute, she perceived all objects within view as rotated 45 degrees clockwise. There were no auras, accompanying symptoms, or sequelae. Neuro-ophthalmic examination findings were normal except for a right relative afferent pupil defect (RAPD). Imaging disclosed a cystic mass in the left posterior thalamus with compression of the brachium of the left superior colliculus. Stereotactic biopsy revealed a pilocytic astrocytoma. This is the first case documenting environmental tilt illusion as an isolated symptom of a thalamic lesion. Disruption of vestibular connections between the posterior thalamus and the posterior parietal cortex may be the cause of this visual perceptive disorder.

Hypothalamic pilocytic astrocytoma presenting with intratumoral and subarachnoid hemorrhage.

A 45-year-old male presented with sudden onset of severe headache. Computed tomography and magnetic resonance imaging demonstrated an irregularly enhanced suprasellar mass with intratumoral and subarachnoid hemorrhage. The mass was removed in two operations. Histological examination of the tumor revealed pilocytic astrocytoma. The relatively rich vascularity and perivascular tumor cell proliferation observed in this benign lesion were probably the causes of this extremely rare association.

Normal evoked otoacoustic emissions with a profound hearing loss due to a juvenile pilocytic astrocytoma.

An interesting case is reported of an 11-year-old girl who experienced a sudden, profound right-sided hearing loss at the age of 5 years after hearing a "pop" and the sound of rushing water in her right ear. At that time the patient was thought to have Mondini's deformity, and a perilymphatic fistula of the oval window in the right ear. Six years later she was diagnosed with a juvenile pilocytic astrocytoma of the pons with an exophytic component extending into the cerebellopontine angle. Of particular interest in this case is the presence of evoked otoacoustic emissions in the right ear with a profound neural hearing loss. The presence of transient evoked and distortion product otoacoustic emissions confirmed normal sensory outer hair cell function and an intact peripheral auditory system in a clinically deaf ear, thus indicating hearing loss due to a neural component instead of a sensory component, which was previously assumed.

Dyshormia revisited: generalized seizures and arousal.

Niedermeyer has described dyshormia, or deviant arousal, and related this EEG pattern to generalized seizures. We describe a patient with generalized seizures who in the same EEG had spindles transforming into generalized epileptiform discharges and generalized epileptiform discharges transforming into spindles. This suggests that similar neural circuitry may underlie both spindles and generalized epileptiform discharges, and that the mechanism described by Gloor for feline generalized penicillin induced epilepsy may also apply to some humans with generalized epilepsies.