Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas.

The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas.

Does "cerebellar liponeurocytoma" always reflect an expected site? An unusual case with a review of the literature.

A rare tumour, cerebellar liponeurocytoma, is classified into glioneuronal tumours under the 2000 World Health Organization (WHO) classification of tumours of the central nervous system. The current 2007 WHO classification, therefore, assigns grade II to the cerebellar liponeurocytoma. Tumours are predominantly localized in cerebellar hemispheres, and the second most common location is the vermis. To date, approximately 40 reported cases of cerebellar and 10 cases of supratentorial intraventricular liponeurocytoma have been reported. In this report, an unusual case of cerebellar liponeurocytoma was presented with extracerebellar location. In the future tumour classification, it should be considered that liponeurocytomas are not restricted only to the cerebellum, but they are located in supratentorial areas as well.

Treatment of brainstem metastases with gamma-knife radiosurgery.

The aim was to investigate the efficacy and safety of gamma-knife stereotactic radiosurgery (SRS) for treating brainstem metastases. The cases of 44 patients who underwent SRS as treatment for 46 brainstem metastases were retrospectively evaluated. The median age was 57 years (range 42-82 years) and the median Karnofsky performance score (KPS) was 80 (range 60-90). The primary tumor was lung carcinoma in 28 cases, breast carcinoma in 7 cases, colon carcinoma in 3 cases, renal cell carcinoma in 3 cases, malignant melanoma in 1 case, and unknown origin in 2 cases. Of the 46 metastases, 30 were in the pons, 14 were in the mesencephalon, and 2 were in the medulla oblongata. The median volume of the 46 metastases was 0.6 cc (range 0.34-7.3 cc). The median marginal dose of radiation was 16 Gy (range 10-20 Gy). Twenty-three patients (52 %) received whole brain radiotherapy prior to SRS, and 6 (14 %) received this therapy after SRS. In the remaining 15 cases (34 %), SRS was applied as the only treatment. Recursive partitioning analysis, graded prognostic assessment, and basic score for brain metastases were used to predict survival time. Local control was achieved for all but two of the 46 metastases (96 %). The overall survival time after SRS was 8 months. Female gender, KPS >70, mesencephalon tumor location, and response to treatment were associated with longer survival. Basic score for brain metastases class I and recursive partitioning analysis classification were associated with better prognosis. Peri-tumoral changes were detected radiologically at 2 (4 %) of the metastatic lesion sites but neither of these patients exhibited symptoms. Gamma-knife radiosurgery is effective for treating brainstem metastases without a higher risk for radiation necrosis.

Current status of neurosurgery in Turkey.

With a population of more than 70 million, Turkey has a large demand for neurosurgery. Neurosurgery is provided by a socialized health care system partly supported by private institutions. There are more than 1200 neurosurgeons practicing in Turkey, and sophisticated surgical procedures are performed in most large cities. Residency training is provided at universities and training hospitals, and the quality of care is supported by two neurosurgical societies.

Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas.

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki-67 (MIB-1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0-3) and intensity (0-3) of immunolabeling of the tumor cells. A high immunohistochemical score (4-6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB-1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow-up period of 47.53 +/- 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB-1 score were significantly higher in recurrent meningiomas than in non-recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas.

Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity.

BACKGROUND: Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, in other words, rerouting nerves proximal to injured cord segments to distal neuromuscular targets, although the underlying mechanisms remain largely unknown. AIM: To test our hypothesis that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows, we anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection in rats. RESULTS: While axonal tracing and electromyography revealed limited reinnervation in the target muscles, neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury (n = 11), recovered to levels close to non-SCI controls with neurotization only (n = 3), beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurotization (n = 7) or 4 weeks-delayed neurotization (n = 3) and in rats that had undergone T13-L1 transection plus bilateral anastomoses (n = 6). CONCLUSION: Neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection stimulates neuroplasticity in the dysfunctional spinal cord. Our conclusion is validated by the fact that severance of the T13-L1 contralateral cord abolished the postanastomosis functional recovery. Neurotization and its neuroplastic sequelae need to be explored further to optimize clinical strategies of post-SCI functional repair.

Congenital dermal sinus of the cervical spine in an adult.

Congenital dermal sinuses are epithelium-lined tracts that extend from an opening in the skin through deeper tissues. Most dorsal congenital dermal sinuses are located in the lumbosacral area; a cervical location is unusual. This report describes a 24-year-old woman who presented with neck pain of 6 months' duration. A dimple in the skin over her cervical spine and a stunted right foot (0.5 cm shorter than the left) were detected on physical assessment. Neurological examination revealed increased deep tendon reflexes in her lower extremities. Magnetic resonance imaging showed a dermal sinus extending from the dimple site to the spinal cord near the C4-C5 vertebrae. Laminectomies were performed at C3-C4 and the tract was totally excised. The patient's neck pain completely resolved and her deep tendon reflexes were normal at 12 months after surgery. Tethered spinal cord alone does not necessarily demand surgery; however, if a congenital dermal sinus is present then surgery is indicated to prevent spinal infection. Even if there are no neurological symptoms, the tract must be surgically removed and the cord must be fully released to prevent future infectious or neurological complications.

Intraspinal gas.

Intraspinal gas can be observed in a number of pathological settings including degenerative disc disease, infection, tumor or trauma, and in patients who have undergone therapeutic and diagnostic procedures. The air can be epidural, intradural or intradiscal. Intraspinal gas is usually asymptomatic. We report intraspinal gas in three patients, one with cervical, one with thoracic, and one with lumber disc disease and spondylolisthesis. The investigations were all completed at the the same medical center and CT and MRI were done in each case. The gas was in the epidural space in all three patients. These cases provide further evidence that intraspinal gas may persist without causing symptoms, and that resultant symptoms can disappear spontaneously. MRI is not reliable for diagnosing intraspinal gas; CT is recommended.

Effects of parenteral fish-oil emulsion (Omegaven) on cutaneous wound healing in rats treated with dexamethasone.

BACKGROUND: The aim was to assess wound healing when parenteral fish-oil emulsion is given to rats receiving dexamethasone. METHODS: For 5 days after skin wounding, group S (control; n = 7) received saline 1 mL/kg intraperitoneal (IP); group D (n = 7), dexamethasone 0.2 mg/kg IP; and group DO (n = 9), dexamethasone 0.2 mg/kg IP plus 1 mL/kg Omegaven (Fresenius Kabi, Austria). Wound specimens were assessed for hydroxyproline level, wound depth, histology (epidermal/dermal regeneration, granulation tissue thickness, and angiogenesis), and expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-AA (PDGF-AA). RESULTS: Compared with D and DO specimens, controls had higher hydroxyproline (p < .01), deeper wounds (p < .05), and better histologic scores (p < .01 angiogenesis; others p < .05). There were no significant differences between the group D and DO means for hydroxyproline level, wound depth, or histologic scores (p > .05 for all). Controls had higher TGF-beta expression scores than the other groups (p < .01 for both) and a higher PDGF-AA expression score than group DO (p < .01). Groups D and DO had statistically similar TGF-beta scores, but group D had a higher PDGF-AA score (2.71 +/- 0.75 vs 1.55 +/- 0.72, respectively; p < .05). CONCLUSIONS: According to the parameters we studied, adding parenteral omega-3 and omega-6 fatty acids to the nutrition regimen of rats treated with dexamethasone does not seem to have adverse effects on wound healing, and effects on wound healing may not need to be considered when determining if these agents should be supplemented in nutrition support regimens.

Foot drop: the first sign of an intracranial tumor?

Isolated foot drop due to a brain lesion is rare. A 48-year-old man complained of inability to dorsiflex the right foot. Right dorsiflexion had 0/5 muscle strength and there were no upper neuron findings on his neurological examination. Magnetic resonance imaging of the brain revealed a left parasagittal brain mass. The lesion was removed and muscle activity returned with 3/5 muscle strength 6 weeks after the operation. The parasagittal area is located at the foot of the homunculus. Therefore, in patients with foot drop, lesions of the parasagittal area should be considered.

Lumbar spinal angiolipoma: case report and review of the literature.

Spinal angiolipomas are extremely rare benign tumors composed of mature lipomatous and angiomatous elements. Most are symptomatic due to progressive spinal cord or root compression. This article describes the case of a 60-year-old woman who presented with a 6-month history of low back pain radiating to her right leg. The pain was multisegmental. The condition had worsened with time. Lumbar magnetic resonance imaging revealed a dorsal epidural mass at L5 and erosion of the lamina of the L5 vertebra. Laminectomy was performed, and an extradural tumor was totally excised. Neuropathologic examination identified it as a lumbar spinal angiolipoma. There was no evidence of recurrence in follow-up 12 months later. This rare clinical entity must be considered in the differential diagnosis for any spinal epidural lesion.

Trigeminal neuralgia due to pontine infarction.

Trigeminal neuralgia (TN) is most commonly caused by vascular compression of the trigeminal nerve root entry zone. Secondary trigeminal neuralgia due to ischemic lesion of the pons is very rare. Here we report a patient with a pontine infarct transecting the central trigeminal pathways resulting with trigeminal neuralgia.

Prophylactic effects of magnesium and vitamin E in rat spinal cord radiation damage: evaluation based on lipid peroxidation levels.

This study investigated the neuroprotective effects of magnesium sulfate prophylaxis and vitamin E prophylaxis in a rat model of spinal cord radiation injury. Groups were subjected to different treatment conditions for 5 days prior to irradiation, and outcomes were evaluated on the basis of lipid peroxidation levels in cord tissue. Four groups of rats were investigated: no radiation/treatment (n = 4), intraperitoneal (i.p.) saline 1 ml/day (n = 6), i.p. vitamin E 100 mg/kg/day (n = 6), and i.p. magnesium sulfate 600 mg/kg/day (n = 6). The thoracic cord of each non-control rat was exposed to 20 Gy radiation in a LINAC system using 6 MV x-rays, and malondialdehyde (MDA) levels (reflecting lipid peroxidation level) were determined 24 hours post-irradiation. The MDA levels in thoracic cord segments from the control rats were used to determine baseline lipid peroxidation. The mean levels in the control, saline-only, vitamin E, and magnesium sulfate groups were 12.12 +/- 0.63, 27.0 +/- 2.81, 17.71 +/- 0.44, and 14.40 +/- 0.47 nmol/mg tissue, respectively. The MDA levels in the saline-only group were significantly higher than baseline, and the levels in the vitamin E group were significantly lower than those in the saline group (P < 0.05 for both). The levels in the magnesium sulfate group were dramatically lower than those in the saline group (P < 0.001). The results indicate that i.p. magnesium sulfate has a marked neuroprotective effect against radiation-induced oxidative stress in the rat spinal cord.

Early-postoperative magnetic resonance imaging in glial tumors: prediction of tumor regrowth and recurrence.

OBJECTIVE: This study investigated the value of early-postoperative magnetic resonance (EPMR) imaging in the detection of residual glial tumor and investigated the role of EPMR for the prediction of tumor regrowth and recurrence. METHODS AND MATERIALS: We retrospectively analyzed pre- and post-operative magnetic resonance imaging results from 50 adult patients who underwent surgical treatment for supratentorial glial tumor. There were glioblastoma multiforme in 25 patients, astrocytoma (grades II and III) in 11 patients, oligodendroglioma (grades II and III) in 9 patients, and oligoastrocytoma (grades II and III) in 5 patients. EPMR imaging was performed within 24 h after surgery. EPMR findings were compared with the neurosurgeon's intraoperative estimation of gross tumor removal. Patterns of contrast enhancement at the resection site, in residual and developing tumor tissue and blood at the resection site were evaluated on EPMR and in follow-up studies. 'Residual tumor' was defined as contrast enhancing mass at the operative site on EPMR. 'Regrowth' was defined as contrast enhancing mass detected on follow-up in the same location as the primary tumor. 'Recurrence' was defined as appearance of a mass lesion in the brain parenchyma distant from the resection bed during follow-up. RESULTS: Nineteen patients showed no evidence of residual tumor, regrowth, or recurrence on EPMR or any of the later follow-up radiological examinations. EPMR identified 20 cases of residual tumor. Follow-up showed tumor regrowth in 10 patients, and tumor recurrence in 1 case. EPMR showed contrast enhancement of the resection bed in 45 of the 50 patients. Four of the 20 residual tumors showed a thick linear enhancement pattern, and the other 16 cases exhibited thick linear-nodular enhancement. No thin linear enhancement was observed in the residual tumor group. Nine of the 10-regrowth tumors showed a thick linear-nodular enhancement pattern, and one exhibited thin linear enhancement in EPMR. For predicting regrowth tumor EPMR sensitivity was 91%, specificity was 100%, positive predictive value 1; negative predictive value was 0.9375. CONCLUSION: EPMR, depending on the surgical site enhancement pattern, is a valuable means of demonstrating residual tumors, and can be used to predict possible regrowth after surgery.