Role of Hemodynamic Forces in Unruptured Intracranial Aneurysms: An Overview of a Complex Scenario.

BACKGROUND: An understanding of the natural history of unruptured intracranial aneurysms (IAs) has always played a critical role in presurgical or endovascular planning, to avoid possibly fatal events. Size, shape, morphology, and location are known risk factors for rupture of an aneurysm, but morphologic parameters alone may not be sufficient to perform proper rupture risk stratification. METHODS: We performed a systematic PubMed search and focused on hemodynamics forces that may influence aneurysmal initiation, growth, and rupture. RESULTS: We included 223 studies describing several hemodynamic parameters related to aneurysm natural history. In these studies, different modalities of aneurysm model creation have been used to evaluate flow and to comprehensively analyze the evolution of IAs. Controversy exists about the correlation between these parameters and initiation, growth, rupture risk, or stabilization of the aneurysmal sac. Recent findings have also shown the importance of flow patterns in this process and the relationship between unruptured IA geometry and hemodynamic parameters. CONCLUSIONS: The role of hemodynamic forces in evaluation of the natural history of unruptured IAs presents is inherently complex and is still not completely understood. In this complex scenario, although several attempts have been described in the literature, a proper risk rupture stratification and treatment strategy selection based on hemodynamic forces has not yet been created. Further efforts should be made to accomplish this important goal.

A rare case of solitary brain Langerhans cell histiocytosis with intratumoral hemorrhage in a patient affected by Turner syndrome.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of cells with characteristics similar to bone marrow-derived Langerhans cells. The case of a young woman, affected by Turner syndrome and a solitary intraparenchymal LCH associated with an osteolytic lesion of the overlying skull, is presented. CASE DESCRIPTION: The patient, with an insidious history of headache and a growing soft mass in the left frontal region, presented with a sudden generalized tonic-clonic epileptic seizure. Neuroradiological investigations showed an osteolytic lesion of the left frontal bone and an underlying brain lesion associated with recent signs of bleeding. The patient was operated on with a complete removal of the lesion. The postoperative course was uneventful. CONCLUSIONS: The clinical, neuroradiological, and intraoperative findings are presented, along with a review of the literature. Although rare, LCH should be considered in the differential diagnosis when a scalp lesion occurs with a progressive growing.

Ossified spinal meningiomas: Clinical and surgical features.

OBJECT: Meningiomas constitute 25% of primary spinal tumors and predominantly involve the thoracic spinal cord. Although calcifications are commonly seen in intracranial meningiomas, gross calcifications are observed in only 1-5% of all spinal meningiomas. We report the clinical findings, surgical strategy and histological features of 9 patients with ossified spinal meningiomas (OSMs). PATIENTS AND METHODS: Clinical and surgical features of 9 patients with ossified spinal meningiomas were retrospectively reviewed. RESULTS: There were 8 women and 1 man with a mean age of 59 years. In 7 patients, the lesions were localized in the thoracic segment of the spine while in 2 patients in the lower cervical segment. All patients presented with weakness of the lower limbs and hypoesthesia below the site level of the lesion. Only 2 patients presented with urinary incontinence. Gross-total resection of the tumor was achieved in 6 patients while in 3 a subtotal removal of the meningioma was obtained. In all patients the postoperative course was uneventful. Six patients presented with a significant neurological improvement while in 3 patients a mild improvement was observed. Microscopically, all tumors showed typical histological pattern of ossified meningioma. CONCLUSIONS: OSMs are amenable to surgery if the complete removal can be achieved. Because of their hard-rock consistency complete resection can be challenging. In difficult cases, subtotal removal can be advised and follow-up imaging is mandatory. Overall, the risk of long-term recurrence of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected.

Spontaneous Meckel's cave hematoma: A rare cause of trigeminal neuralgia.

BACKGROUND: The most common etiology of classic trigeminal neuralgia (TN) is vascular compression. However, other causes must be considered. Among these, spontaneous hematoma of the Meckel's cave (MC) causing symptomatic TN is very rare. CASE DESCRIPTION: We present the case of a 60-year-old woman with a 2-month history of left TN and diplopia. Neuroradiological examinations revealed a well-defined hematoma in the left MC. The patient underwent surgical decompression with a progressive neurological improvement. CONCLUSION: Despite the number of lesions potentially affecting the MC, spontaneous hemorrhage is rare but should be taken into account in the differential diagnosis.

Cavernous malformation of the optic chiasm: An uncommon location.

BACKGROUND: Cavernous malformations (CMs) of the optic chiasm are rare lesions often presenting with acute chiasmal syndrome or a progressive visual loss. The case of a 48-year-old female with an intrachiasmatic CM is presented. CASE DESCRIPTION: The patient presented with an insidious history of progressive visual loss. Magnetic resonance imaging (MRI) showed a CM in the suprasellar region. The patient was operated via a right pterional approach with a complete lesion removal. The postoperative course was uneventful. Early postoperative ophthalmological examination revealed minimal improvement of the vision in the left eye. CONCLUSION: The clinical, neuroradiological, and intraoperative findings are presented, along with a review of the literature.

Presurgical evaluation of hemifacial spasm and spasmodic torticollis caused by a neurovascular conflict from AICA with 3T MRI integrated by 3D drive and 3D TOF image fusion: A case report and review of the literature.

BACKGROUND: Hemifacial spasm (HS) and spasmodic torticollis (ST) are well-known disorders that are caused by a neurovascular conflict. HS is characterized by irregular, involuntary muscle contractions on one side of the face due to spasms of orbicularis oris and orbicularis oculi muscles, and is usually caused by vascular compression of the VII cranial nerve. ST is an extremely painful chronic movement disorder causing the neck to involuntary turn to the side, upward and/or downward. HS is usually idiopathic but it is rarely caused by a neurovascular conflict with the XI cranial nerve. CASE DESCRIPTION: We present a case of a 36-year-old woman with a 2-year history of left hemifacial spasm and spasmodic torticollis. Pre-surgical magnetic resonance imaging MRI examination was performed with 3TMRI integrated by 3Ddrive and 3DTOF image fusion. Surgery was performed through a left suboccipital retrosigmoid craniectomy. The intraoperative findings documented a transfixing artery penetrating the facial nerve and a dominant left anteroinferior cerebellar artery (AICA) in contact with the anterior surface of the pons and lower cranial nerves. Microvascular decompression (MVD) was performed. Postoperative course showed the regression of her symptoms. CONCLUSIONS: Transfixing arteries are rarely reported as a cause of neurovascular conflicts. The authors review the literature concerning multiple neurovascular conflicts.

Large trigeminal schwannoma of the infratemporal fossa: evaluation of neoangiogenesis in this rare neoplasm.

BACKGROUND: Trigeminal schwannomas are uncommon intracranial tumors. Extracranial trigeminal schwannomas in the infratemporal fossa are rare. METHODS: We present a case with a clinical history of facial pain. MRI and CT scans showed a mass arising from the infratemporal fossa extending into the intracranial space. RESULTS: We performed a combined neurosurgical and maxillofacial approach with preoperative endovascular embolization. Complete removal of the parasellar component was achieved with a minimal extracranial neoplastic residual. High microvessel density, reflecting intense neoangiogenesis, was detected through the immunohistochemical staining with endoglin. CONCLUSIONS: Due to the unique development pattern of trigeminal schwannoma involving multiple intracranial fossae and extracranial compartment, we chose a combined neurosurgical and maxillofacial approach with preoperative embolization of the tumor. Immunohistochemical findings suggest that the extensive growth observed may be related to an intense neoangiogenesis, opening the perspective to novel therapeutic options based on the inhibition of neoangiogenesis.

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.

Aneurysm clipping following endovascular coil embolization: a report of two cases.

BACKGROUND: Treatment of intracranial aneurysms by Guglielmi detachable coil (GDC) embolization is a useful therapeutic alternative to surgery. This procedure is attractive as a minimally invasive approach to treat cerebral aneurysms; however, is not devoid of complications or failure and retreatment, with either a surgical or endovascular technique, may often be required. CASE REPORTS: Two cases are presented in which surgery was required after coil embolization. In one case, surgical treatment was performed one month later because of regrowth and subsequent bleeding of the aneurysm. In the second case, surgical treatment was carried out six months later because of recanalization of the vascular malformation. Surgical treatment excluded both aneurysms from the cerebral circulation. CONCLUSIONS: In this paper the authors illustrate their experience and underline the difficulty of aneurysm surgery with coils in place.

Bulbar compression by an ectatic vertebral artery: a novel neurovascular construct relieved by microsurgical decompression.

OBJECTIVE: Brainstem compression caused by vascular abnormalities has rarely been reported in the literature. We describe five cases of large ectatic vertebral artery causing compression and distortion of the medulla oblongata with pyramidal tract signs and low cranial nerve dysfunction. Microvascular decompression by retracting the vertebral artery and anchoring it to the dura has been the treatment of choice. METHODS: Five patients, four male and one female, presented with progressive myelopathic features and lower cranial nerve dysfunction, especially dysphonia and dysphagia. Four patients were affected by systemic arterial hypertension. Magnetic resonance imaging showed impingement of the right vertebral artery in three patients and the left vertebral artery in two patients, on the right and left lateral medulla, respectively. In two patients, hypoplasia of the contralateral vertebral artery was documented. RESULTS: All patients underwent neurovascular decompression of the medulla oblongata. The ectatic and tortuous vertebral artery was detached from the medulla, shifted away, and repositioned by anchoring to the nearby dura mater using a Gore-Tex vascular slip. Postoperatively, all patients but one had improvement of their previous neurological symptoms. CONCLUSION: Brainstem dysfunction caused by a tortuous ectatic vertebral artery might be less uncommon than expected. It should be considered a new distinct clinical entity, the real incidence of which needs to be carefully evaluated by an appropriate diagnostic protocol, which includes primarily magnetic resonance imaging with specific three-dimensional sequences. Awareness of this condition is necessary to ensure the appropriate treatment. Surgical microvascular decompression seems very effective.

Landmarks for vertebral artery repositioning in bulbar compression syndrome: anatomic and microsurgical nuances.

OBJECTIVE: The purpose of this study was to better elucidate the anatomic relationship between the vertebral artery (VA) along with its perforating vessels and the brainstem to develop anatomic guidelines that would be helpful when decompressing medulla oblongata compressed by the VA. METHODS: Microanatomy dissection was performed in six formalin-fixed cadaveric heads. The VA, posteroinferior cerebellar artery (PICA), anteroinferior cerebellar artery (AICA), and lower brainstem perforators were examined under magnification using a surgical microscope. The outer diameters of the VA, PICA, and AICA were measured. The distance between the VA, lying within the lateral cerebellomedullary cistern, and the medulla oblongata was quantified. The lower brainstem perforating vessels were examined in relation to their course, outer diameter, and length. RESULTS: In four of six brains, the left VA was dominant, presenting an outer diameter at least 0.8 mm larger than the contralateral VA. The average distance between the VA and the medulla oblongata was 3 mm. The perforating branches presented a mean outer diameter of 0.7 mm. In particular, perforators arising from the VA and PICA (Groups 1 and 2) presented an average outer diameter of 0.2 mm and an average length of 7 mm. Perforating vessels arising from the AICA and vertebrobasilar junction (Groups 3 and 4) presented an average outer diameter of 0.4 mm and an average length of 12 mm. CONCLUSION: This work provides new information that may be useful to minimize the risk of injury of perforators when operating on medulla oblongata compression by the VA.

Cerebellar hematoma in a patient with Marfan syndrome.

BACKGROUND: Marfan syndrome is a connective tissue disorder affecting many structures, including the skeleton, lungs, eyes, heart and blood vessels. It is an autosomal dominant inherited disorder due to a mutation of a gene encoding fibrillin-1, which affects connective tissue. Few case reports have associated Marfan syndrome with vascular malformations of the brain and spinal cord. In this regard, association with intracranial aneurysm has been vaguely proposed. CASE REPORT: We report here a patient with Marfan syndrome who was admitted because of a sudden loss of consciousness. The patient underwent computed tomography (CT) examination, which disclosed a right intracerebellar hematoma. Cerebral angiogram did not demonstrate aneurysm or arteriovenous malformation (AVM), or evidence of any other vascular lesions or neoplasms in the posterior fossa. Conservative treatment was undertaken. The clinical course was uneventful and after 6 weeks the patient was discharged free of symptoms. CONCLUSIONS: Although patients with Marfan syndrome are at high risk of vascular abnormalities, a clear association with cerebral aneurysm has not yet been established. Our experience and the contrasting reports available in the medical literature strongly warrant further studies in order to better clarify this controversial association.

Assessment of human brain water content by cerebral bioelectrical impedance analysis: a new technique and its application to cerebral pathological conditions.

OBJECTIVE: Total brain water content changes in several cerebral pathological conditions and the measurement of brain water content are important for the selection of appropriate therapeutic procedures. We present a quantitative, in vivo, bioelectrical impedance analysis (BIA) method and propose its use for the accurate assessment of brain water content among human subjects. METHODS: Cerebral BIA is based on the conduction of an applied current in the brain parenchyma. Application of an excitatory current of 800 microA at 50 kHz, via two electrodes placed on the eyelids with the eyes closed, and detection of the voltage drop with two electrodes placed in the suboccipital region allow brain resistance and reactance to be measured. By means of an equation that considers cranial circumference and resistance, it is possible to quantify the total brain water content, expressed as the bioelectrical volume. Cerebral BIA was performed with a series of healthy volunteers (n = 100), for determination of average brain water content values. The method was then applied to 50 patients with brain tumors (n = 20), intracranial hemorrhage (n = 16), or hydrocephalus (n = 14), for assessment of changes in global brain water contents. Data were compared with those obtained for healthy volunteers. RESULTS: Statistically significant differences (P < 0.001) were observed between the two groups. Mean brain water content values (expressed as bioelectrical volume values) were 38.2 +/- 3.9 cm2/Omega for healthy volunteers and 67.7 +/- 13.1 cm2/Omega for patients with cerebral pathological conditions. Statistically significant differences (P < 0.05) were also observed among patients with cerebral pathological conditions. CONCLUSION: The results of this study suggest that BIA, applied to the cerebral parenchyma, is a valid method for the prediction of brain water contents under both normal and pathological conditions. However, further studies are needed to establish whether it is sensitive and reliable enough for future clinical applications.

Beneficial effects of systemic administration of recombinant human erythropoietin in rabbits subjected to subarachnoid hemorrhage.

Cerebral vasospasm and ischemic damage are important causes of mortality and morbidity in patients affected by aneurysmal subarachnoid hemorrhage (SAH). Recently, i.p. administration of recombinant human erythropoietin (r-Hu-EPO) has been shown to exert a neuroprotective effect during experimental SAH. The present study was conducted to evaluate further the effect of r-Hu-EPO administration after SAH in rabbits on neurological outcome, degree of basilar artery spasm, and magnitude of neuronal ischemic damage. Experimental animals were divided into six groups: group 1 (n = 8), control; group 2 (n = 8), control plus placebo; group 3 (n = 8), control plus r-Hu-EPO; group 4 (n = 8), SAH; group 5 (n = 8), SAH plus placebo; group 6 (n = 8), SAH plus r-Hu-EPO. r-Hu-EPO, at a dose of 1,000 units/kg, and placebo were injected i.p. starting 5 min after inducing SAH and followed by clinical and pathological assessment 72 h later. Systemic administration of r-Hu-EPO produced significant increases in cerebrospinal fluid EPO concentrations (P < 0.001), and reduced vasoconstriction of the basilar artery (P < 0.05), ischemic neuronal damage (P < 0.001), and subsequent neurological deterioration (P < 0.05). These observations suggest that r-Hu-EPO may provide an effective treatment to reduce the post-SAH morbidity.