Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature.

Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFß and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors' proliferative index (Ki67) increased from 5-6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

Pituitary pathology in traumatic brain injury: a review.

PURPOSE: Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors, hypopituitarism is a common complication. RESULTS: Pituitary dysfunction occurs in approximately 20-40% of patients diagnosed with moderate and severe traumatic brain injury giving rise to growth hormone deficiency, hypogonadism, hypothyroidism, hypocortisolism, and central diabetes insipidus. Varying degrees of hypopituitarism have been identified in patients during both the acute and chronic phase. Anterior pituitary hormone deficiency has been shown to cause morbidity and increase mortality in TBI patients, already encumbered by other complications. Hypopituitarism after childhood traumatic brain injury may cause treatable morbidity in those survivors. Prospective studies indicate that the incidence rate of hypopituitarism may be ten-fold higher than assumed; factors altering reports include case definition, geographic location, variable hospital coding, and lost notes. While the precise pathophysiology of post traumatic hypopituitarism has not yet been elucidated, it has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage. A number of mechanisms have been proposed to clarify the causes of primary mechanical events giving rise to ischemic adenohypophysial infarction and the ensuing development of hypopituitarism. CONCLUSION: Future research should focus more on experimental and clinical studies to elucidate the exact mechanisms behind post-traumatic pituitary damage. The use of preventive medical measures to limit possible damage in the pituitary gland and hypothalamic pituitary axis in order to maintain or re-establish near normal physiologic functions are crucial to minimize the effects of TBI.

Paradoxical results obtained with Ki67-labeling and PHH3-mitosis index in glial tumors: a literature analysis.

Precise tiered tumor grading is essential for predicting prognosis, selecting different treatment options and for follow-up of brain tumor patients. Ki67 labeling index (LI) is widely employed in assessing aggressiveness of glial brain tumors. However, Ki67 is subject to interlaboratory variability, and its antigen is expressed on all cell cycle phases except G0, which hinders its usage as a precise criterion for assessing cell proliferation. Indeed, there exist peculiar observations pertinent to increases of Ki67 index in glial tumors following radiotherapy or treatment with tyrosine kinase inhibitors. Moreover, we have witnessed a reduced Ki67 labeling in a gemistocytic glioma during its rapid recurrence under temozolomide treatment. Therefore, we reviewed pitfalls in employing Ki67 indices for predicting glial tumor biology and tried to answer whether the mitotic marker PHH3 (phosphorylated histone H3) could provide additional information in predicting glial tumor biology. PHH3-based assessment of proliferating cell fraction provides novel potentials, but it has also its own weaknesses. It has not yet been determined whether it would be more advantageous to report: a mitotic count (MC) per unit-area (e.g., 10 high power fields (HPF)) or a mitotic index (MI) (per 1,000 tumor cells). Further, there exist peculiarities in terms of unexpectedly low or high PHH3 values in pilocytic astrocytomas and angiocentric gliomas, respectively. Indeed, we encountered almost no staining with PHH3 in our unique gemistocytic astrocytoma case. Hence, at least in some glial malignancies, PHH3 may not be necessary for cell proliferation. Awareness of the weaknesses of proliferation markers in brain tumors may improve patient monitoring and treatment.
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Impact of 1p/19q codeletion on the diagnosis and prognosis of different grades of meningioma.

BACKGROUND: Meningiomas are one of the most common tumours to affect the central nervous system. Genetic mutations are important in meningeal tumourigenesis, progression and prognosis. In this study, we aimed to examine the effect of 1p/19q deletion on the diagnosis and prognosis of meningioma subtypes using the fluorescence in situ hybridization (FISH) method. METHODS: Twenty-four patients with meningioma were retrospectively studied. Tumour samples were obtained from 10 typical, 11 atypical and three anaplastic malignant meningiomas. The most representative tumour sections were screened for 1p/19q deletion using the FISH method. RESULTS: Of the 24 patients, eight were women (33.3%) and 16 (66.7%) were men. The mean age was 56.6 years. The higher-grade meningioma was usually seen in males and had a higher rate of deletion on 1p (p = 0.001). There was a statistically significant difference between the grades and the rate of deletion on 19q (p = 0.042) and between the grades and the rates of polysomy, monosomy and amplification on 19q (p = 0.002; p = 0.001; p = 0.002, respectively). There was no statistical difference between 1p/19q codeletion and the grades of meningioma (p > 0.05). We detected higher level of Ki-67 in the condition of codeletion but did not find a statistical difference (p = 0.0553). CONCLUSION: Deletion on 1p, as well as deletion, polysomy, monosomy and amplification on 19q, are detected more frequently in high grade meningiomas. This amplification is most likely due to the amplification of oncogenes.

Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series.

OBJECTIVE: The authors report on a large, consecutive, single-surgeon series of patients undergoing microsurgical removal of midbrain gliomas. Emphasis is put on surgical indications, technique, and results as well as long-term oncological follow-up. METHODS: A retrospective analysis was performed of prospectively collected data from a consecutive series of patients undergoing microneurosurgery for midbrain gliomas from March 2006 through June 2022 at the authors' institution. According to the growth pattern and location of the lesion in the midbrain (tegmentum, central mesencephalic structures, and tectum), one of the following approaches was chosen: transsylvian (TS), extreme anterior interhemispheric transcallosal (eAIT), posterior interhemispheric transtentorial subsplenial (PITS), paramedian supracerebellar transtentorial (PST), perimedian supracerebellar (PeS), perimedian contralateral supracerebellar (PeCS), and transuvulotonsillar fissure (TUTF). Clinical and radiological data were gathered according to a standard protocol and reported according to common descriptive statistics. The main outcomes were rate of gross-total resection; extent of resection; occurrence of any complications; variation in Karnofsky Performance Status score at discharge, 3 months, and last follow-up; progression-free survival (PFS); and overall survival (OS). RESULTS: Fifty-four patients (28 of them pediatric) met the inclusion criteria (6 with high-grade and 48 with low-grade gliomas [LGGs]). Twenty-two tumors were in the tegmentum, 7 in the central mesencephalic structures, and 25 in the tectum. In no instance did the glioma originate in the cerebral peduncle. TS was performed in 2 patients, eAIT in 6, PITS in 23, PST in 16, PeS in 4, PeCS in 1, and TUTF in 2 patients. Gross-total resection was achieved in 39 patients (72%). The average extent of resection was 98.0% (median 100%, range 82%-100%). There were no deaths due to surgery. Nine patients experienced transient and 2 patients experienced permanent new neurological deficits. At a mean follow-up of 72 months (median 62, range 3-193 months), 49 of the 54 patients were still alive. All patients with LGGs (48/54) were alive with no decrease in their KPS score, whereas 42 showed improvement compared with their preoperative status. CONCLUSIONS: Microneurosurgical removal of midbrain gliomas is feasible with good surgical results and long-term clinical outcomes, particularly in patients with LGGs. As such, microneurosurgery should be considered as the first therapeutic option. Adequate microsurgical technique and anesthesiological management, along with an accurate preoperative understanding of the tumor's exact topographic origin and growth pattern, is crucial for a good surgical outcome.

Cerebral Erdheim-Chester disease mimicking high-grade glial tumor: a case report.

Erdheim-Chester disease (ECD) is a non-Langerhans histiocytosis. It may present in every organ in the body, but isolated central nervous system involvement, especially a supratentorial intra-axial location, is extremely rare. We present a case of ECD of supratentorial intra-axial origin and discuss the clinical presentation, diagnosis and management strategies.

Whorling Sclerosing Ependymoma of the Cervical Spinal Cord Presenting Tanycytic Histopathologic Features: A Rare Case Report.

Tanycytic ependymoma is a neuroectodermal tumor that arises from ependymoglial cells or tanycytes. It is highly uncommon. We reported a 34-year-old man who was diagnosed with intradural-intramedullary tanycytic ependymoma, located at the level of C4-5 who had a 9-months history of neck pain and left arm pain, and numbness on fingers. One month prior to presentation, his left arm numbness and paresthesia deteriorated. The lesion was removed totally by C4, C5 hemilaminoplasty. The histologic pattern of this lesion was consisted of fascicles forming nebula-like whorling structures. Because of these structures, tanycytic ependymoma should be taken into consideration in the differential diagnosis of a whorling-sclerosing variant of meningiomas.

The effect of 2 different distraction-compression models on new bone generation.

PURPOSE: To compare the stimulating effect of distraction and 2 different distraction-compression models on maturation of new bone during healing. MATERIALS AND METHODS: Thirty adult Sprague-Dawley rats underwent unilateral mandibular osteotomy. The animals were divided into 3 groups. A unidirectional external distraction device was fixed to the mandible. A total of 4 mm of distraction was planned in all groups. After a latency period of 3 days, 0.2 mm of distraction was performed twice a day for 10 days in the distraction group. In the intermittent distraction-compression group, 0.2 mm of distraction was performed twice a day for 3 days, followed by 0.2 mm of compression twice a day for 1 day. In the overdistraction-compression group, 0.2 mm of distraction was performed twice a day for 14 days, followed by 0.2 mm of compression twice a day for 4 days. After a consolidation period of 6 weeks in all groups, animals were killed for macroscopic, microscopic, and radiologic evaluation. RESULTS: Radiologic evaluation proved that more mature bone generation occurred in the groups in which compression was added to distraction. The number of osteoblasts in the intermittent distraction-compression group was significantly higher than that in the distraction group and overdistraction-compression group (P < .001). The highest number of vessels was found in the intermittent distraction-compression group (17.7 ± 6.4) (P < .001). CONCLUSIONS: The intermittent distraction-compression model was found to generate greater new bone compared with distraction alone. In clinical applications, to increase the quality of the bone and to shorten the consolidation period, compression can be applied during distraction.

Serial EEG and MRI changes in status epilepticus-induced excitotoxic neuronal necrosis.

Prolonged status epilepticus may directly cause selective neuronal necrosis due to excitotoxic mechanisms, as observed in experimental models and described in case reports. A 36-year-old woman presented with right hemiplegia and aphasia following a generalised tonic-clonic status epilepticus of two hours duration. Accompanying serial MRI with advanced imaging techniques, EEG and histopathology of the cortical tissue of the patient were all compatible with excitotoxic neuronal necrosis. In this histopathologically-proven rare case of status epilepticus-induced excitotoxic neuronal injury, the observation of delayed cortical laminar necrosis on MRI, together with paroxysmal lateralised epileptiform discharges on the EEG, suggests that these changes may be an early sign of impending and ongoing excitotoxic neuronal injury and delayed cell death caused by glutamate release due to excessive neuronal firing in status epilepticus.

Induction of HGF and VEGF in hepatic regeneration after hepatotoxin-induced cirrhosis in mice.

BACKGROUND/AIMS: Liver cirrhosis is the irreversible end-result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of normal hepatic structure by regenerative nodules and fibrotic tissue. In this study, we elucidated the role of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in liver regeneration. METHODOLOGY: The study was conducted as an experimental laboratory investigation using a mouse model of lethal liver cirrhosis induced by carbon tetrachloride (CCl4), dimethylnitrosamine (DMN) and D-galactosamine (D-gal) administrations. RESULTS: Liver morphology showed fibrosis/cirrhosis in all groups, but to a different extent, as confirmed by the rise in serum transaminase levels. The immunolocalization of VEGF and HGF, and homogenate levels of HGF and serum levels of VEGF, were also analyzed. Liver fibrosis/cirrhosis was more severe in CCl4-treated mice. In cirrhotic livers, immunostaining for HGF was weak and the HGF content of liver tissue was lower. Strong immunoreactivity for VEGF was observed when hepatotoxins were administered, however as cirrhosis became apparent immunoreactivity was reduced. Blood VEGF levels increased gradually. CONCLUSIONS: Our results suggest possible involvement of VEGF in angiogenesis of cirrhotic liver. VEGF might be required for reconstruction of hepatic cells and sequentially participates in liver regeneration by facilitating hepatocyte proliferation. HGF production is supposed to be induced in the necrotic liver during regeneration and severe tissue damage followed by cirrhosis might account for low homogenate HGF levels.

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case.

BACKGROUND: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. METHODS: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. RESULTS: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. CONCLUSIONS: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.

Hypothalamitis: A Novel Autoimmune Endocrine Disease. A Literature Review and Case Report.

CONTEXT: The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic-pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate. EVIDENCE ACQUISITION: Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia. EVIDENCE SYNTHESIS: Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported. CONCLUSIONS: We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism.

Lipofibromatous hamartoma of the median nerve.

Lipofibromatous hamartoma is a rare tumor-like overgrowth of fibroadipose tissue surrounding the nerves. Most commonly, it involves the median nerve. The tumor is usually present at birth and grows very slowly. The expected age of clinical presentation is the third or fourth decades of life. The case reported here had a rapid overgrowth and presented at the age of eight. Our case is the first reported case of lipofibromatous hamartoma of the median nerve in the pediatric age group.

Methanol intoxication: pathological changes of central nervous system (17 cases).

The nervous system has increased susceptibility for methanol intoxication. The aim of this study is to investigate various central nervous system lesions of methanol intoxication in 17 cases autopsied in the mortuary department of the Council of Forensic Medicine in Istanbul, Turkey. The reasons of methanol intoxication in the cases was likely the unwitting ingestion of methanol while drinking illegal alcohol. Survival times ranged from several hours to days. In 8 cases (47%), cerebral edema and in 9 cases (53%) at occipital, temporal and parietal cortex, basal ganglia and pons, petechial bleeding was observed. In addition to these findings, hemorrhagic necrosis were observed in thalamus, putamen, and globus pallidus in 5 cases (29.4%) and, in cerebral cortex in another 3 cases (17.6%). In 3 of the cases (17.6%) in which cerebral edema was found, herniation findings accompanied to the situation and in 2 cases (11.7%), pons bleeding was observed. Around the basal ganglia, in 2 of the cases with hemorrhagic necrosis, the situation ended with a ventricular compression. In 7 cases (41%), the associated findings of chronic ischemic changes in cortical neurons, lacunae formation, degeneration of granular cell layer of the cerebellum, and reactive gliosis were considered as the results of chronic alcoholism.

Isocitrate dehydrogenase (IDH) status prediction in histopathology images of gliomas using deep learning.

Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary glioblastomas. As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient's treatment. However, H&E staining alone does not determine the IDH mutational status of a tumour. Deep learning methods applied to MRI data have been demonstrated to be a useful tool in IDH status prediction, however the effectiveness of deep learning on H&E slides in the clinical setting has not been investigated so far. Furthermore, the performance of deep learning methods in medical imaging has been practically limited by small sample sizes currently available. Here we propose a data augmentation method based on the Generative Adversarial Networks (GAN) deep learning methodology, to improve the prediction performance of IDH mutational status using H&E slides. The H&E slides were acquired from 266 grade II-IV glioma patients from a mixture of public and private databases, including 130 IDH-wildtype and 136 IDH-mutant patients. A baseline deep learning model without data augmentation achieved an accuracy of 0.794 (AUC = 0.920). With GAN-based data augmentation, the accuracy of the IDH mutational status prediction was improved to 0.853 (AUC = 0.927) when the 3,000 GAN generated training samples were added to the original training set (24,000 samples). By integrating also patients' age into the model, the accuracy improved further to 0.882 (AUC = 0.931). Our findings show that deep learning methodology, enhanced by GAN data augmentation, can support physicians in gliomas' IDH status prediction.

Late brain stem radionecrosis seventeen years after fractionated radiotherapy.

The appearance of a new lesion several years after radiation treatment for a primary brain tumor may represent different kind of pathologies. We present a 24-year-old patient who suffered from right-sided hemiparesis and ataxic gait with a history of an operation due to left frontoparieal grade II fibrillary astrocytoma and fractioned radiotherapy. His cranial MRI study showed heterogeneous signal intensity of brain stem radionecrosis in the pons spreading through the mesencephalon and left brachium pontis. The leading diagnosis was high-grade glial tumor. The patient underwent stereotaxic biopsy and histopathological examination revealed radionecrosis. Radiation necrosis has a radiological appearance similar to various important pathologies. Tissue sampling for histopathological examination is mandatory for definite diagnosis and correct treatment of the disease.

Intradiploic meningioma mimicking calvarial metastasis: case report.

Meningiomas are the most common benign intracranial neoplasms. Nearly 20% of all primary intracranial tumors are meningiomas. Primary intraosseous meningiomas are a subtype of the meningiomas that represents the most uncommon manifestation of meningiomas. Although rare, these tumors can be found to occur in unexpected areas of the head and neck. The patient was a 78- year-old male who was operated two times for urinary bladder cancer. During his routine oncology follow-ups, the PET scan demonstrated a hyperactive area in the right parietal bone. Preoperative diagnosis was a metastasis, but histological examination revealed an osteolytic interosseous meningioma. The possibility of an intraosseous meningioma mimicking a metastatic tumor should be kept in mind.