Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Calcifications associated with pediatric intracranial arterial aneurysms: incidence and correlation with pathogenetic subtypes.

BACKGROUND AND PURPOSE: Little is known about calcifications associated with pediatric intracranial arterial aneurysms (IAA). We sought to characterize calcifications associated with pediatric IAA according to aneurysm pathogenetic subtype. MATERIALS AND METHODS: Patients with IAA less than 20 years of age were retrospectively identified. Three fellowship-trained neuroradiologists independently reviewed each patient's CT studies for calcifications of the parent artery or aneurysm. Aneurysmal calcification (ANC) was correlated with characteristics of the patient (age, sex) and aneurysm pathogenetic subtype, size, morphology, rupture status, and location. RESULTS: Thirty-three patients (mean age 10 years) with 43 IAA were analyzed. There were no parent artery calcifications. Nine IAA were calcified. IAA in children with non-hemodynamic risk factors (arteriopathy, trauma, infection, tumor) were more commonly calcified than idiopathic IAA (p = 0.029). More than one third of the pediatric IAAs in this group (arteriopathy, infection trauma, tumor) were calcified. IAA ≥ 10 mm were more likely to be calcified (p = 0.03). IAA that were ruptured at presentation were less likely to be calcified (p = 0.03). ANC was not significantly associated with patient age (≤10 years vs. >10 years), sex, morphology (fusiform vs. saccular) or location (anterior vs. posterior circulation). CONCLUSION: Aneurysmal but not parent artery calcifications are associated with a significant minority of pediatric IAA. Pediatric ANCs are associated with underlying non-hemodynamic vascular risk factors (arteriopathy, infection, trauma, and tumor), size ≥10 mm and non-hemorrhagic presentation.

Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial.

INTRODUCTION: Compared to ischemic stroke, intracerebral hemorrhage (ICH) is easily and rapidly identified, occurs in younger patients, and produces relatively small initial injury to cerebral tissues--all factors suggesting that interventional amelioration is possible. Investigations from the last decade established that extent of ICH-mediated brain injury relates directly to blood clot volume and duration of blood exposure to brain tissue. Using minimally-invasive surgery plus recombinant tissue plasminogen activator (rtPA), MISTIE investigators explored aggressive avenues to treat ICH. METHODS: We investigated the difference between surgical intervention plus rtPA and standard medical management for ICH. Subjects in both groups were medically managed according to standard ICU protocols. Subjects randomized to surgery underwent stereotactic catheter placement and clot aspiration. Injections of rtPA were then given through hematoma catheter every 8 h, up to 9 doses, or until a clot-reduction endpoint. After each injection the system was flushed with sterile saline and closed for 60 min before opening to spontaneous drainage. RESULTS: Average aspiration of clots for all patients randomized to surgery plus rtPA was 20% of mean initial clot size. After acute treatment phase (aspiration plus rtPA), clot was reduced an average of 46%. Recorded adverse events were within safety limits, including 30-day mortality, 8%; symptomatic re-bleeding, 8%; and bacterial ventriculitis, 0%. Patients randomized to medical management showed 4% clot resolution in a similar time window. Preliminary analysis indicates that clot resolution rates are greatly dependent on catheter placement. Location of ICH also affects efficacy of aggressive treatment of ICH. CONCLUSION: There is tentative indication that minimally-invasive surgery plus rtPA shows greater clot resolution than traditional medical management.

Multidrug-resistant, progressive, invasive diffuse spinal aspergillosis: case report and review of the literature.

The authors describe a 65-year-old man who, after 7 years of complete remission from lung cancer, was found on routine oncologic follow imaging to have lesions on several vertebral bodies. Open biopsy of the affected thoracic vertebrae and surrounding soft tissue were negative for neoplasia. Bacteriology cultures revealed colonies of aspergillus fumigatus in all bone samples. Unlike most reported cases in which vertebral compromise rarely extends to more than two adjacent vertebrae, our patient had extensive compromise of the thoracic spine. This infection progressed despite treatment with antifungal regimens known to be effective, even in immunocompromised patients. Invasive aspergillosis of the spine is a rare and typically occurred in terminal patients. However, the spectrum of hosts and clinical presentations of invasive aspergillosis are increasing, due in part to better medical treatments that prolong the survival of patients with cancer, severe infections, and organ failure. In reviewing the literature, the authors discuss the currently available therapies for such infections of the spine, and highlight the growing incidence these and other formerly rare infections.

Evidence-based surgical treatment of carotid stenosis. Literature review.

Carotid stenosis is an important cause of transient ischemic attacks and stroke. The cause of carotid stenosis is most often atherosclerosis, which accounts for 10% to 20% of brain infarction cases. Despite the introduction of tissue-plasminogen activator and other promising experimental therapies for select patients with acute ischemic stroke prevention remains the best approach to reduce its impact. Stroke-prone patients can be identified and targeted for specific interventions. At this juncture, treatment of carotid stenosis is a well-established therapeutic target and a pillar of stroke prevention. Two main strategies exist for the treatment of carotid stenosis. The 1st is stabilization or halting the progression of the carotid plaque formation with medications and modifications of risk factors (e.g., hypertension, diabetes, smoking, obesity, high cholesterol). The 2nd approach is the elimination or reduction of carotid stenosis by carotid endarterectomy or angioplasty and stenting. Carotid endarterectomy is the mainstay of therapy for symptomatic, severe carotid stenosis. Although its role for asymptomatic patients appears more limited, it is distinct for severe stenosis. Carotid angioplasty and stenting are techniques in maturation with the attractiveness of being less invasive that face the challenge of at least replicating the results of surgery. In this article, we will discuss the surgical management of symptomatic and asymptomatic carotid stenosis based on the evidence provided by the literature.

Aneurysms of the ophthalmic (C6) segment of the internal carotid artery: treatment options and strategies based on a clinical series.

AIM: Treatment of ophthalmic segment aneurysms is technically demanding and still associated with a relatively high morbidity and mortality. The refinements of surgical techniques combined with the development of indirect methods of treatment have greatly improved the outcome in treating these lesions. We present our clinical experience and discuss treatment strategies. METHODS: Seventy-eight consecutive patients with 88 ophthalmic segment aneurysms were admitted to our service from January 1997 to June 2003. Forty-three patients presented with unruptured aneurysms and 35 presented with subarachnoid hemorrhage (SAH). Management strategies included surgical clipping alone in 53 patients, clipping and hemicraniectomy in 2, coiling in 17, external carotid artery-middle cerebral artery (ECA/MCA) by-pass in 2, and coil occlusion of the internal carotid artery in 2. Two patients underwent no treatment. RESULTS: In the group of 41 treated patients with unruptured aneurysms, 40 (97.6%) had good outcomes (GOS 1-2) and 1 patient had poor (GOS 3) outcome at discharge. Procedure-related morbidity was 15.7% (8/51 procedures), and permanent morbidity was 9.75% (4/41 patients). In the 35 patients who presented with SAH, mortality was 14.3% (5 patients); at discharge, 21 patients (60%) had good (GOS 1-2) and 9 (25.7%) poor (GOS 3) outcomes. The overall outcome was good (GOS 1-2) in 63 patients (80.8%) and poor (GOS 3-4) in 10 patients (12.8%). Overall mortality was 6.4% (5 patients all with SAH). CONCLUSIONS: Direct obliteration of the aneurysm utilizing advanced surgical techniques is our preferred treatment approach, whenever possible. In case of unclippable large or giant aneurysms, the surgical or endovascular occlusion of the proximal internal carotid artery with or without an extracranial-intracranial by-pass is an option. A highly skilled team including a cerebrovascular and an endovascular surgeon is essential to achieve good outcomes in treating these lesions.

Visceral leishmaniasis and HIV co-infection: a rare case of pulmonary and oral localization.

Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in countries bordering the Mediterranean sea. The clinical course as well as organ involvement of VL are often atypical in HIV positive subjects. In this study a case of VL with pulmonary and oral mucose localisation in a patient with acquired immune deficiency syndrome (AIDS), is reported. These findings, together with the presence of the parasite in the peripheral blood smear, confirm that in HIV positive patients the impaired immune system allows the spreading and the atypical localisation of the Leishmania amastigotes more easily than in immuno-competent individuals. In endemic areas and in HIV positive subjects a systemic and careful parasitological follow-up is necessary to ensure that any clinical form of leishmaniasis is not overlooked.

Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery.

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) has been shown to be effective for acute ischemic stroke. However, if a high-grade cervical carotid stenosis remains despite tPA therapy, patients are at risk for recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in symptomatic patients with high-grade cervical carotid stenosis in reducing the risk of stroke, but it is unknown whether CEA can be performed safely after tPA thrombolysis. We describe our experience with 5 patients who underwent early (<48 hours) CEA for residual high-grade cervical carotid stenosis after thrombolytic therapy for acute ischemic stroke in the middle cerebral artery territory. METHODS: All patients had a critical (>99%) carotid artery stenosis on the symptomatic side after tPA therapy. All patients received intravenous tPA; 3 patients also received intra-aortic tPA. Three patients received intravenous heparin infusion immediately after administration of tPA. All patients showed marked improvement in their National Institutes for Health Stroke Scale scores after treatment with tPA. CEA was then performed within 45 hours (6 hours in 1 patient, 23 hours in 2, 26 hours in 1, and 45 hours in 1). RESULTS: All 5 patients underwent successful CEA. There were no complications related to surgery. At discharge, 2 patients had a normal examination, and the remaining patients had mild deficits. In a long-term follow-up of 5 to 22 months, no patient had a recurrent cerebrovascular event. CONCLUSIONS: Early CEA can be performed safely and successfully in patients after tPA treatment for acute ischemic stroke in appropriately selected patients.

Expanding the boundaries of the transsphenoidal approach: a microanatomic study.

The anatomic features of a transsphenoidal approach are reviewed, focusing on the microsurgical anatomy of parasellar structures. Pertinent microsurgical anatomy is described in sufficient detail for the neurosurgeon to successfully extend a standard transsphenoidal approach for treatment of lesions involving the region of the tuberculum sellae, planum sphenoidale, supradiaphragmatic intradural space, and medial cavernous sinus. The parasellar region of 50 formalin-fixed cadaveric heads was examined by using magnification 3x to 40x. The arterial and venous systems of five cadaveric specimens were injected under pressure with colored silicone rubber. The sellar region of three specimens was examined histologically. Important anatomic landmarks identified in the roof of the sphenoid sinus include a carotid and trigeminal prominence, as well as a tubercular, clival, and opticocarotid recess. The diaphragma sella is actually comprised of two layers of dura, with a venous system (circular sinus) interposed between the layers. The dura mater of the pituitary gland separates the gland from the medial compartment of the cavernous sinus. The microanatomic detail necessary to extend the transsphenoidal approach to the supradiaphragmatic intradural space and medial compartment of the cavernous sinus is described. These data are presented to facilitate the clinical application of these extended approaches.

Treatment strategy for patients with unruptured intracranial aneurysms.

The increased sensitivity of neuroimaging techniques has enabled the more frequent diagnosis of unruptured aneurysms. Because the most devastating complication of an unruptured aneurysm is subarachnoid hemorrhage, it has been considered desirable to treat these aneurysms before they rupture. However, the optimal treatment strategy for patients with unruptured aneurysms remains controversial. The management decision requires knowledge of the natural history and an accurate assessment of the risks related to various treatment options. On December 10, 1998 the New England Journal of Medicine published an article by the International Study of Unruptured Intracranial Aneurysms Investigators. The study retrospectively assessed the natural history of unruptured aneurysms in 1449 patients; in addition, treatment-related mortality and morbidity were examined in a prospective cohort of 1172 patients. The major finding was that the rate of rupture for aneurysms smaller than 10 mm in diameter in patients with no history of subarachnoid hemorrhage was 0.05% per year, and that the mortality and morbidity associated with surgery greatly exceeded the risk of rupture in such patients. This report has generated tremendous controversy in the treatment of unruptured aneurysms and has influenced our decision making. The results of this study are critically analyzed and potential flaws presented. To develop recommendations for treatment, the literature was reviewed. The conclusion of this search is that there is insufficient evidence to recommend a standard of management. Therapeutic guidelines are provided, particularly for patients with small incidental aneurysms and no history of subarachnoid hemorrhage.

Intraoperative magnetic resonance imaging to determine the extent of resection of pituitary macroadenomas during transsphenoidal microsurgery.

OBJECTIVE: Well-established surgical goals for pituitary macroadenomas include gross total resection for noninvasive tumors and debulking with optic chiasm decompression for invasive tumors. In this report, we examine the safety, reliability, and outcome of intraoperative magnetic resonance imaging (iMRI) used to assess the extent of resection, and thus the achievement of preoperative surgical goals, during transsphenoidal microneurosurgery. METHODS: Our magnetic resonance operating room contains a Hitachi AIRIS II 0.3-T, vertical-field open magnet (Hitachi Medical Systems America, Inc., Twinsburg, OH). A motorized scanner tabletop moves the patient between the imaging and operative positions. For transsphenoidal surgery, the patient is positioned directly on the scanner tabletop so that the surgical field is located between 1.2 and 1.6 m from the magnet isocenter. At this location, the magnetic field strength is low (<20 G), thus permitting the use of many conventional surgical instruments. Thirty consecutive patients with pituitary macroadenomas underwent tumor resection in our magnetic resonance operating room by use of a standard transsphenoidal approach. After initial resection, the patient was advanced into the scanner for imaging. If residual tumor was demonstrated and deemed surgically accessible, the patient underwent immediate re-exploration. RESULTS: iMRI was performed successfully in all 30 patients. In one patient, iMRI was used to clarify the significance of hemorrhage from the sellar region and resulted in immediate conversion of the procedure to a craniotomy. In the remaining 29 patients, initial iMRI demonstrated that the endpoint for extent of resection had been achieved in only 10 patients (34%) after an initial resection attempt, whereas 19 patients (66%) still had unacceptable residual tumor. All 19 of these latter patients underwent re-exploration. Ultimately, re-exploration resulted in the achievement of the planned endpoint for extent of resection in all of the 29 completed transsphenoidal explorations. Operative time was extended in all cases by at least 20 minutes. CONCLUSION: iMRI can be used to safely, reliably, and objectively assess the extent of resection of pituitary macroadenomas during the transsphenoidal approach. The surgeon is frequently surprised by the extent of residual tumor after an initial resection attempt and finds the intraoperative images useful for guiding further resection.

Angiolipomas of the central nervous system.

Angiolipomas are neoplasms composed of mature adipocytes admixed with abnormal vascular elements. They are most commonly found in the subcutaneous tissue of the trunk and extremities, but other sites have been reported. The craniospinal axis is an uncommon but significant site. An extensive review of the literature is conducted. We summarize 94 cases of angiolipomas in the central nervous system (CNS) in 92 patients, including five in our own series, to highlight the most prominent features of these tumors. The increasing number of cases of CNS angiolipoma in the era of magnetic resonance imaging raises the question of the rarity of these lesions.

Cervical subarachnoid hematoma of unknown origin: case report.

OBJECTIVE AND IMPORTANCE: Spontaneous spinal subarachnoid hematoma is rare, having been reported in the English literature in only seven other cases. We describe the first case of spontaneous subarachnoid hematoma located in the cervical spinal cord of a 43-year-old man. The pathologic examination showed no apparent source of bleeding, but there was evidence of cervical spondylotic myelopathy. CLINICAL PRESENTATION: The patient presented with a 10-day history of severe neck pain, followed by the onset of quadriparesis that was more evident on the left side, urinary retention, and sensory loss below C5. His medical history included hypertension. Magnetic resonance imaging showed a massive hemorrhage in the cervical spinal canal. INTERVENTION: A C4-C5 subarachnoid hematoma was removed. The patient died due to respiratory distress and uncontrollable hypotension on day 6 after surgery. Surgical exploration, neuroradiologic examinations, and autopsy showed no evidence of vascular malformations, tumors, or other possible sources of bleeding. CONCLUSION: After excluding more common causes of spontaneous subarachnoid hematoma in this patient, we suggest that chronic spinal cord compression (spondylotic myelopathy) and arterial hypertension in this patient may have caused the pathogenesis of this rare clinical entity. Experimental data supporting this hypothesis are discussed.

Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study.

BACKGROUND AND PURPOSE: The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH. METHODS: Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm(3) on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3. RESULTS: Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14; P=0.04). CONCLUSIONS: Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.

Sarcoidosis en-plaque. Report of a case and review of the literature.

A 31-year-old black male with sarcoidosis en-plaque of the dura mater, which is a rare morphological variant of neurosarcoidosis (NS), presented at our clinic. Magnetic resonance imaging (MRI) of the head with gadolinium showed non-specific enhancement of both tentorial leaves extending to the floor of right middle cranial fossa and cavernous sinus. The laboratory results were normal except for slightly increased serum angiotensin converting enzyme (SACE) (68 U/ml n = 4-56 U/ml) and cerebrospinal fluid (CSF) IgG index (0.57, n = 0.46). Biopsy of the intracranial dural lesion was consistent with sarcoidosis. Oral steroid therapy (Methylprednisolone 4 mg QID) was started and the patient became asymptomatic. However, MRI of the brain with gadolinium 2 months after biopsy showed progression and extension of the enhanced dural lesion. His SACE level was unchanged. We concluded that progression of the enhanced lesion seen in MRI could be recently formed scar tissue, new lesion or both. MRI findings should always be correlated with clinical findings for evaluation of NS during follow-up.

Oligodendroglial hamartoma of the right temporal lobe: a case report and discussion of possible histogenesis.

A case of oligodendroglial hamartoma is reported in a 39-year-old man with a 20-year history of petit mal seizures. Magnetic Resonance Imaging of the brain showed a small focal area of abnormal decreased signal on T1-weighted images of the right temporal lobe. The patient became seizure free after the removal of the lesion and treatment with carbamazepine. Pathologic examination revealed several aggregates of oligodendroglial cells with small, dark, regularly stained nuclei and a clear, well-defined perinuclear halo; there was no mixture of neurons or astrocytes. Although these cells were negative, the background was strongly positive for glial fibrillary acidic protein, and myelin basic protein. The histopathologic diagnosis of the temporal lobe lesion was oligodendroglial hamartoma. This report documents an additional subtype of temporal lobe hamartoma associated with seizure disorder.

Brain metastasis from endometrial carcinoma. Report of two cases.

The authors report two cases of surgically treated brain metastases from endometrial cancer which are quite unusual occurrences. In one of them the brain lesion was the presenting symptom of malignancy while in the other the metastasis was discovered after the primary tumor had been treated. Both the brain lesions were scarcely differentiated adenocarcinomas which closely resembled the uterine primaries histologically. The authors review the four cases reported in the literature and discuss the clinical features and the treatment of this disease. The analysis of cases shows that the metastatic potential of endometrial cancer is extremely variable and unpredictable but less severe than that observed in ovarian or cervical tumors. The authors suggest that the erratic behaviour of endometrial cancer may justify an aggressive (though necessarily palliative) approach to brain metastases even in the presence of circumscribed metastatic involvement.

Interaction between free radicals and excitatory amino acids in the blood-brain barrier disruption after iron injury in the rat.

Excitatory amino acids and oxygen free radicals have been reported to cooperate in the genesis of brain injury in vivo and in vitro. In this study, we tested the capacity of a noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801, and a 21-aminosteroid, U-74006F, tirilazad mesylate, to block the opening of the blood-brain barrier after subarachnoid injection of FeCl2, which is believed to cause a primarily "pure" free radical insult. Subarachnoid injection of FeCl2 resulted in a significant 10-fold increase in Evans blue extravasation while sham injection or NaCl injection had no effect. Pretreatment with either MK-801 or U-74006F significantly reduced the FeCl2-induced increase in capillary permeability by 43 and 63%, respectively (p < 0.05). Combined treatment with MK-801 and U-74006F resulted in a 65% reduction in vascular leakage that was not significantly greater than pretreatment with either drug alone. These results show that both excitatory amino acids and free radicals can damage the cerebral microvasculature and that an excitatory amino acid antagonist can partially protect the blood-brain barrier after free radical-induced injury.

Recovery of vision after transcranial decompression of pituitary apoplexy characterized by third ventricular hemorrhage.

The authors present a case of pituitary apoplexy characterized by massive third ventricular hemorrhage. This rare complication, which caused total blindness in the patient, a 67-year-old man, was treated with transcranial decompression of the pituitary tumor and removal of a blood clot from the third ventricle. After surgery, the patient totally recovered his vision. To the best of our knowledge, this is the first case of a patient with pituitary apoplexy that ruptured into the third ventricle (diagnosed by imaging studies) who was treated by emergency transcranial decompression.