Idiopathic normal pressure hydrocephalus diagnosis: Quantitative and qualitative score predicting outcome of extended lumbar drainage.

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Cyberknife radiosurgery for cranial plasma cell tumor.

Cranial and intracranial involvement by myelomatous disease is relatively uncommon. Furthermore, systemic manifestations of multiple myeloma are present in the majority of these cases at the time of symptom onset. The authors report the case of a patient with serial appearance of multiple intracranial plasma cell tumor localizations as the first manifestations of a multiple myeloma. The patient was treated with CyberKnife radiosurgery for a lesion localized at the clivus and sella turcica with complete local control. With such a technique, based on high-dose conformality, the tumor was centered with an ablative dose of radiation and, at the same time, with a low dose spreading to the surrounding critical structures. The radiosensitivity of plasma cell tumors renders this treatment modality particularly advantageous for their localized manifestation. A technical description of this case is provided. To our knowledge, this is the first case of successful Cyberknife radiosurgery of multifocal intracranial plasmacytoma.

Nanoparticle-based cerebral drug-delivery systems and antiangiogenic approach in gliomas treatment.

The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.

Could nanoparticle systems have a role in the treatment of cerebral gliomas?

Malignant brain tumors are difficult to manage clinically and are associated with high rates of morbidity and mortality. Late diagnosis and the limitations of conventional therapies that may result from inefficient delivery of the therapeutic or contrast agent to brain tumors due to the blood-brain barrier and nonspecificity of the agents, are major reasons for this unsolved clinical problem. Nanotechnology involves the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer scale. The nanoparticle has emerged as a potential vector for brain delivery, able to overcome the difficulties of modern strategies. Moreover, multifunctionality can be engineered into a single nanoplatform so that it can provide tumor-specific detection, treatment, and follow-up monitoring. This review reports the latest research in nanoparticle-based glioma treatment. FROM THE CLINICAL EDITOR: In recent years, nanoparticles have emerged as potential delivery vectors targeting brain tumors, including multifunctional NP-s allowing tumor-specific detection, treatment, and follow-up monitoring. This review summarizes the latest research in nanoparticle-based glioma treatment.

Penetrating head injury by a stone: case report and review of the literature.

Traumatic intracranial penetration of foreign objects of non-missile intracranial nature rarely occurs. Haemorrhages, major vascular injury and contusions can be causes of death in early stage, epileptic seizures and infections are possible complications in later stages. Complete excision of the foreign body should be performed. Possible dural and vascular injuries should be repaired during surgical treatment. In the present study, we report a rare case of traumatic intracranial stone as a foreign object. A brief review of the literature is presented.

Nanotechnology platforms in diagnosis and treatment of primary brain tumors.

Despite aggressive multimodal strategies, the prognosis in patients affected by primary brain tumors is still very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells into the cerebral parenchyma when they interact with the extracellular matrix via cell surface receptors. The major problem in drug delivery into the brain is due to the presence of the blood brain barrier which limits drug penetration. Nanotechnology involves the design, synthesis and characterization of materials that have a functional organization at least in one dimension on the nanometer scale. Nanoengineered devices in medical applications are designed to interface and interact with cells and tissues at the molecular level. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors, across the blood brain barrier. In this brief review, we report the results of studies related to the emerging novel applications of nanoparticle systems in diagnosis and treatment of primary brain tumors, and also the patents of studies that adopt nanoparticle systems as drug delivery carriers in brain tumor diagnosis and therapy.

Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas.

Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

Immunohistochemical study of the extracellular matrix proteins laminin, fibronectin and type IV collagen in secretory meningiomas.

The extracellular matrix plays a pivotal role in numerous cellular functions during normal and pathological processes. Secretory meningiomas are rare histological meningioma subtypes that have benign behavior, are highly vascularized and are frequently accompanied by massive peritumoral edema. The aim of this study was to assess in secretory meningiomas the immunohistochemical expression of laminin, fibronectin and type IV collagen, proteins found in the extracellular matrix. Extracellular matrix proteins were evaluated in samples from six secretory meningiomas using a semiquantitative scale ranging from not detected (0) to marked (3). Laminin expression was not detected in two cases, but was minimal in one, moderate in one and marked in the remaining cases. Fibronectin expression was absent in two cases, minimal in two, moderate in one and marked with generalized distribution in the remaining case. Type IV collagen expression was minimal in three cases, moderate in two and marked with generalized distribution in the remaining case. Our results are indicative of significant neoangiogenic activity. Meningiomas increase in size through increased production of extracellular matrix; furthermore, the proliferation of cells typically associated with neoplasia requires considerable interaction with the extracellular matrix.

NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.

Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectrophotofluorimetric technique 2 days post-injury). Animals were injected with 400 muL of autologous blood into the cisterna magna. Within 5 min, rats received daily oral administration of FBM (15, 30, or 45 mg/kg) for 2 or 5 days. Results were compared with sham-injured controls treated with oral saline or FBM (15, 30, or 45 mg/kg). FBM administration significantly ameliorated SAH-related changes in Beam Balance scores on days 1 and 2 and Beam Balance time on days 1-3, Beam Walking performance on days 1 and 2, and Body Weight on days 3-5. FBM also decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This study demonstrates that, in terms of behavioral and microvascular effects, FBM is beneficial in a dose-dependent manner after experimental SAH in rats. These results reinforce the concept that NMDA excitotoxicity is involved in the cerebral dysfunction that follows SAH.

CD68 and CR3/43 immunohistochemical expression in secretory meningiomas.

OBJECTIVE: Secretory meningiomas (SMs) are unusual benign meningiomas. SMs are highly vascularized lesions, with angiomatous features and a perivascular arrangement, and they are accompanied frequently by massive peritumoral edema. Microglia have been called the brain's immune system, although the specific role and prognostic significance of microglia remain uncertain. The objective of this study was to analyze the expression of CD68, a macrophage marker specific for resting microglia, and the expression of major histocompatibility complex Class II CR3/43 in SMs. METHODS: From 1995 to 2002, six patients with SMs were treated surgically at our institution. Immunohistochemistry was used to analyze the expression of CD68 and CR3/43 in tumor specimens. The intensity of expression was graded semiquantitatively. A correlation between immunohistochemical expression and the occurrence of brain edema was studied. RESULTS: CD68-positive mononuclear cells were observed in neoplastic tissue or around pseudopsammoma bodies and in perivascular areas, with minimal expression in one patient and moderate expression in three patients. CR3/43-positive complexes were detected in mononuclear elongated elements with ameboid extensions, presumably referable to cells at different stages of immunological activation phenomena, with minimal expression in two patients, moderate expression in one patient, and marked expression in one patient. Edema was severe in all patients. Therefore, it may be indirectly hypothesized that edema may not be correlated with the CD68 and CR3/43 immunohistochemical expression. CONCLUSION: Macrophage infiltration and major histocompatibility complex Class II immunoreactivity in this subtype of meningioma suggest the occurrence of an immune response in the presence of SM.

The treatment of large supratentorial arachnoid cysts in infants with cyst-peritoneal shunting and Hakim programmable valve.

OBJECTIVE: This retrospective case series examines 7 infants with large supratentorial arachnoid cysts who underwent cyst-peritoneal shunting and insertion of a Hakim programmable valve. Comparing pre- and postoperative clinical data, neuroradiological and regional cerebral blood flow (rCBF) findings we evaluated the efficacy of the surgical procedure. METHODS: Infants, ranging in age from 1 to 55 days (mean age 29.5 days), were assessed pre- and postoperatively by neurological examination, developmental profile and neuroimaging. RESULTS: Post procedure, all patients showed a significant reduction in the cyst/brain ratio on neuroimaging (p<0.001), 6 had a normal developmental profile (p<0.001) and 5 cases showed a significant amelioration of clinical symptoms and neurological signs. Two patients underwent preoperative SPECT scans, which showed hypoperfusion in the area surrounding the cyst; this decreased rCBF also improved post shunting. CONCLUSIONS: Large supratentorial arachnoid cysts in infants can be successfully treated with cyst-peritoneal shunting and insertion of a Hakim programmable valve. This is the first study specifically aimed at evaluating the long-term results of these conditions.