Molecular Sequence of Events and Signaling Pathways in Cerebral Metastases.

Brain metastases are the leading cause of morbidity and mortality among cancer patients, and are reported to occur in about 40% of cancer patients with metastatic disease in the United States of America. Primary tumor cells appear to detach from the parent tumor site, migrate, survive and pass through the blood brain barrier in order to establish cerebral metastases. This complex process involves distinct molecular and genetic mechanisms that mediate metastasis from these primary organs to the brain. Furthermore, an interaction between the invading cells and cerebral milieu is shown to promote this process as well. Here, we review the mechanisms by which primary cancer cells metastasize to the brain via a mechanism called epithelial-to-mesenchymal transition, as well as the involvement of certain microRNA and genetic aberrations implicated in cerebral metastases from the lung, breast, skin, kidney and colon. While the mechanisms governing the development of brain metastases remain a major hindrance in treatment, understanding and identification of the aforementioned molecular pathways may allow for improved management and discovery of novel therapeutic targets.

Spinal Cord Compression Secondary to Extramedullary Hematopoiesis: Case Report and Review of the Literature.

Extramedullary hematopoiesis (EMH) is a rare cause of spinal cord compression (SCC). EMH represents the growth of blood cells outside of the bone marrow and occurs in a variety of hematologic illnesses, including various types of anemia and myeloproliferative disorders. Although EMH usually occurs in the liver, spleen, and lymph nodes, it may also occur within the spinal canal. When this occurs, the mass effect can compress the spinal cord, potentially leading to the development of neurological deficits. We present a case of SCC secondary to EMH. This report illustrates the importance of considering EMH in the differential diagnosis of SCC, even in the absence of signs of its most common etiologies.

Traumatic Lumbar Subdural Hematoma in the Absence of Intracranial Disease.

BACKGROUND: Traumatic spinal subdural hematoma is an exceedingly rare condition, with those occurring in the absence of intracranial disease being particularly uncommon. Only 13 such cases have been reported. Although theories exist to describe the pathophysiology of traumatic spinal subdural hematoma, the precise mechanism and guidelines for management remain unclear. CASE DESCRIPTION: This report describes a 37-year-old woman who suffered a traumatic assault who developed progressive low back pain with radicular symptoms 2 days after presentation. Magnetic resonance imaging revealed a lumbar subdural hematoma extending from L1 to L5. No intracranial disease was detected on imaging. CONCLUSIONS: Definitive guidelines for management of this condition are uncertain; however, successful use of conservative management, lumbar drainage, and surgical evacuation has been reported. This patient underwent a lumbar laminectomy with evacuation of the hematoma, resulting in immediate pain relief and resolution of symptoms within 1 week of the procedure.

Malignant carotid body tumor presenting with myelopathy: case report.

Malignant carotid body tumors are rare, with spread of the tumor mostly noted in regional lymph nodes. Vertebral metastases are an exceedingly rare presentation, only reported in isolated case reports, and present a diagnostic and management challenge. A case of widespread vertebral metastasis, presenting with myelopathy, from a carotid body tumor is discussed in this paper, along with management strategies.

Delayed Tension Pneumocephalus following Gunshot Wound to the Head: A Case Report and Review of the Literature.

Tension pneumocephalus is a rare complication of head trauma and neurosurgical procedures, amongst other causes. It is defined by the combination of intracranial air, increased intracranial pressure, and mass effect. Although it often presents soon after surgery, it can also rarely present in a delayed fashion. We present a case of delayed tension pneumocephalus, occurring approximately 16 weeks after bifrontal craniectomy for a self-inflicted gunshot wound. Following a month of rhinorrhea, postnasal drip, and cough, the patient presented with a sensation of expansion in the area of the right forehead. As tension pneumocephalus is an emergency that can be fatal, this patient was treated expediently and avoided severe neurological deficits. The case recounted here is important as a demonstrative example that tension pneumocephalus does not always follow a defined course immediately after trauma or neurosurgery but rather can develop insidiously without obvious signs.

Intracranial hemorrhage in patient treated with rivaroxaban.

Rivaroxaban is an oral factor Xa inhibitor used for stroke prevention in atrial fibrillation. There are currently no evidence-based guidelines for the treatment of hemorrhagic side effects of factor Xa inhibitors. We report a case of a thalamic hemorrhage in an 84 year-old right-handed female on rivaroxaban for treatment of atrial fibrillation. The patient had fallen down steps and became unresponsive. She was found to have diffuse scattered acute subarachnoid hemorrhage as well as intraventricular hemorrhage. Neurosurgical intervention was not required in this case, but controversy over decision making to pursue pro-coagulant therapy in the setting of worsening hemorrhage requiring emergent surgery is discussed.

Use of allograft bone for posterior C1-2 fusion.

OBJECT: An iliac crest autograft is the gold standard for bone grafting in posterior atlantoaxial arthrodesis but can be associated with significant donor-site morbidity. Conversely, an allograft has historically performed suboptimally for atlantoaxial arthrodesis as an onlay graft. The authors have modified a bone grafting technique to allow placement of a bicortical iliac crest allograft in an interpositional manner, and they evaluated it as an alternative to an autograft in posterior atlantoaxial arthrodesis. METHODS: The records of 89 consecutive patients in whom C1-2 arthrodesis was performed between 2001 and 2005 were reviewed. RESULTS: Forty-seven patients underwent 48 atlantoaxial arthrodeses with an allograft (mean follow-up 16.1 months, range 0-49 months), and 42 patients underwent autograft bone grafting (mean follow-up 17.6 months, range 0-61.0 months). The operative time was 50 minutes shorter in the allograft (mean 184 minutes, range 106-328 minutes) than in the autograft procedure (mean 234 minutes, range 154-358 minutes), and the estimated blood loss was 50% lower in the allograft group than in the autograft group (mean 103 ml [range 30-200 ml] vs mean 206 ml [range 50-400 ml], respectively). Bone incorporation was initially slower in the allograft than in the autograft group but equalized by 12 months postprocedure. The respective fusion rates after 24 months were 96.7 and 88.9% for autografts and allografts. Complications at the donor site occurred in 16.7% of the autograft patients, including 1 pelvic fracture, 1 retained sponge, 1 infection, 2 hernias requiring repair, 2 hematomas, and persistent pain. CONCLUSIONS: The authors describe a technique for interpositional bone grafting between C-1 and C-2 that allows for the use of an allograft with excellent fusion results. This technique reduced the operative time and blood loss and eliminated donor-site morbidity.

Inhibition of x-irradiation-enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol.

OBJECT: Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. METHODS: Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. CONCLUSIONS: These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

Perineural spread of malignant mesothelioma resulting in an intradural spinal cord mass: case report.

Spinal cord involvement by perineural spread of malignant mesothelioma is rare. We report a case of malignant mesothelioma that spread locally to invade the bony spine with both extradural and intradural perineural spread into the spinal canal that resulted in spinal cord compression. A 61-year-old man with a history of malignant mesothelioma presented with progressive leg weakness and right-sided arm weakness. Magnetic resonance imaging showed an enhancing lesion in the apex of the right lung with extension through the C7-T1 foramina with right hemicord enhancement. The patient underwent a C7-T1 laminectomy and right-sided C7-T1 and T1-T2 foraminotomies for neural decompression and biopsy of the lesion. Intraoperatively, tumor extended epidurally, and intradural perineural tumor spread along the C8 and T1 nerve roots into the spinal cord. Because it adhered to the spinal cord, no dissectible plane could be identified that would allow for safe total removal of the tumor. The epidural portion of the tumor, the adjacent involved bone, and the T1 nerve root were resected. Pathologic examination revealed malignant mesothelioma with bony invasion and perineural spread along the T1 nerve root. After decompression of the spinal cord, the patient had moderate improvement of his hand and leg function. Perineural spread of malignant mesothelioma resulting in spinal cord compression is an unusual clinical presentation. Intimate involvement of the spinal cord may prohibit aggressive tumor resection.

Comparison of polyetheretherketone cages with femoral cortical bone allograft as a single-piece interbody spacer in transforaminal lumbar interbody fusion.

OBJECT: Transforaminal lumbar interbody fusion (TLIF) is an accepted alternative to circumferential fusion of the lumbar spine in the treatment of degenerative disc disease, spondylolisthesis, and recurrent disc herniation. To maintain disc height while arthrodesis takes place, the technique requires the use of an interbody spacer. Although titanium cages are used in this capacity, the two most common spacers are polyetheretherketone (PEEK) cages and femoral cortical allografts (FCAs). The authors compared the clinical and radiographic outcomes of patients who underwent TLIF with pedicle screw fixation, in whom either a PEEK cage or an FCA was placed as an interbody spacer. METHODS: The charts and x-ray films obtained in 39 patients (age range 33-68 years, mean 44.7 years) who underwent single-level TLIF between October 2001 and April 2004 and in whom either a PEEK cage (18 patients) or FCA (21 patients) was placed as an interbody spacer were evaluated in a retrospective study. Radiological outcome was based on fusion rate and a comparison of the initial postoperative lordotic angle on standing lateral radiographs with that at long-term follow up (mean follow up 15.1 months, minimum 12 months). To control for variations in radiographic magnification, the authors used lordotic angle as an indirect measure of disc space height. Clinical outcome was assessed using the Oswestry Disability Index (ODI). There were no major complications in either group. Radiographically documented fusion occurred in all patients in the PEEK group and 95.2% of those in the FCA group. Pseudarthrosis developed in one patient in the FCA group, and this patient underwent additional surgery. In both groups, the mean lordotic angle changed by less than 2.20 degrees during the postoperative period, and the mean postoperative ODI score was more than 40 points lower than the mean preoperative score. There was no significant difference between the two groups in mean change in lordotic angle (p = 0.415) and mean change in ODI score (p = 0.491). CONCLUSIONS: Both PEEK cages and FCAs are highly effective in promoting interbody fusion, maintaining postoperative disc space height, and achieving desirable clinical outcomes in patients who undergo TLIF with pedicle screw fixation. The advantages of PEEK cages include a lower incidence of subsidence and their radiolucency, which permits easier visualization of bone growth.

Surgical management of cervical myelopathy: indications and techniques for multilevel cervical discectomy.

BACKGROUND CONTEXT: Surgery is usually required for treatment of cervical myelopathy to decompress the neural elements, restore lordosis, and stabilize the spine. By addressing these problems, the neurological deterioration may be halted. PURPOSE: Multilevel cervical discectomy and fusion offers several advantages over other approaches. The authors describe the technique, discuss the indications, and present the potential complications associated with it. METHODS: Decompression is achieved via discectomy and subsequent removal of the osteophytes using a curetting technique. Preparation of end plates in a parallel fashion allows for gapless grafting of allograft bone for enhancement of fusion. A dynamic plate and screw system strengthens the construct. RESULTS: A high rate of fusion can be obtained using the technique of multilevel cervical discectomy and fusion with acceptable levels of complications. It is especially useful in cases of spondylosis that have a kyphotic deformity because, in addition to anterior decompression, it allows reconstruction of the spine to help restore a lordotic curvature. CONCLUSIONS: Multilevel cervical discectomy and fusion has proven to be very effective in decompressing and stabilizing the spine for treatment of cervical myelopathy.

Meningioangiomatosis associated with neurofibromatosis: report of 2 cases in a single family and review of the literature.

BACKGROUND: Meningioangiomatosis (MA) is a rare benign disorder. It may occur sporadically or in association with neurofibromatosis (NF). The sporadic type typically presents with seizures, whereas that associated with NF is often asymptomatic. Of the 100 cases reported, only 14 are associated with NF. We now report 2 additional cases of MA associated with neurofibromatosis 2 (NF2) in a single family, with one occurring in the cerebellum. The etiology, pathology, and imaging features of MA are presented. CASE DESCRIPTION: A 38-year-old woman (patient 1) presented with a 4-month history of ataxia. She had been diagnosed previously with NF2. Magnetic resonance imaging (MRI) scans of the brain revealed bilateral acoustic neuromas and multiple calcified intracranial lesions. Her 13-year-old daughter (patient 2) presented with complex partial seizures. MRI scans of the brain revealed bilateral acoustic neuromas and a right parietal mass. Patient 1 underwent a suboccipital craniotomy to resect the right-sided acoustic neuroma. A small portion of normal-appearing cerebellar cortex was resected to avoid undue retraction. Histopathologic examination showed the presence of a lesion consistent with MA. Patient 2 underwent a right temporal-parietal craniotomy to remove the enhancing epileptogenic right posterior temporoparietal lesion. Histopathologic analysis showed a lesion consistent with meningioma and MA. CONCLUSIONS: MA has been reported infrequently in association with NF2. We now report 2 cases of MA associated with NF2 in one family, and we add the cerebellum to possible locations of occurrence. MA should be considered in the differential diagnosis of cortical lesions, particularly in patients with NF2.

History of instrumentation for stabilization of the subaxial cervical spine.

In the past several decades methods have been developed to stabilize the subaxial cervical spine both posteriorly and anteriorly. Methods of posterior stabilization have progressed from interspinous wiring, through facet wiring and sublaminar wiring, to the lateral mass screws with plates and rods that are in use today. Plates for anterior stabilization have evolved from rigid plates requiring bicortical screws through those used with unicortical locking screws, to dynamic load-sharing plates used with variable angle screws. The original description of spinous process wiring was published by Hadra in 1891. In 1942 Rogers described the interspinous wiring method used for trauma-induced cervical instability, which was modified by Bohlman in 1985 (triple wiring technique). Luque rods with sublaminar wires were introduced in the late 1970s to address multilevel and occipitocervical instability. Facet wiring was developed in 1977 by Callahan to address the problem of stabilization when laminae are not present. Wiring remained the method used until Roy-Camille introduced the lateral mass screw-plate construct in the 1980s. The first plate for anterior stabilization was designed by Orozco and Llovet in 1970 and was later refined by Caspar; this was a rigid plate with bicortical screws. Morscher devised unicortical locking screws in the 1980s. The latest concept of dynamic load-sharing plates with variable angle screws was developed in 2000. In this article historical landmarks in surgical methods for the stabilization of the subaxial cervical spine are reviewed.

Tempol, a nitroxide antioxidant, improves locomotor and histological outcomes after spinal cord contusion in rats.

We have determined whether the nitroxide antioxidant, tempol, can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight-drop device and locomotor recovery was determined with the 21-point Basso, Beattie and Bresnahan (BBB) scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater in tempol-treated (275 mg/kg i.p., 20 min postinjury) compared to vehicle-treated rats (final BBB scores: 9.1 versus 6.4). Similarly enhanced locomotor recovery was observed with doses of tempol in the range of 138-550, but not 69 mg/kg, and with injection at 48 h postinjury indicating a therapeutic time-window of at least several days. The extent of recovery correlated with measurements of sparing of spinal cord white matter in a region several millimeters in length extending rostrally from the contusion epicenter. In contrast, loss of gray matter was unaffected by tempol treatment. Since tempol acts by scavenging reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, the improved locomotor recovery and spared spinal cord tissue following contusion injury provides evidence of a direct role of ROS-mediated neurodegeneration in spinal cord injury.

Widespread central nervous system cavernous malformations associated with café-au-lait skin lesions. Case report.

The simultaneous presence of cavernous malformations in the brain and spinal cord is a very rare finding and is typically associated with familial cavernous malformations. Although they are uncommon, various skin lesions can manifest in patients with familial cavernous malformations. The authors report on a 60-year-old man in whom more than 100 lesions consistent in appearance with cavernous malformations, including several intramedullary spinal cord lesions, were found throughout the neuraxis. This patient also displayed prominent café-au-lait skin lesions, but had no additional signs of neurofibromatosis or other neurocutaneous disorders. Analysis of his DNA revealed a novel mutation in the KRIT1/CCM1 gene, thereby confirming the diagnosis of familial cavernous malformation. The presence of these lesions in every major compartment of this patient's central nervous system underscores their indiscriminate nature and the need to screen throughout the neuraxis in patients in whom familial cavernous malformations are suspected. The findings in this case add to the growing list of skin lesions associated with genetically confirmed familial cavernous malformations. In patients presenting with seizures, focal neurological deficits, or hemorrhagic stroke, the presence of unusual skin lesions should prompt consideration of familial cavernous malformations, and appropriate screening should be performed.

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

BACKGROUND: Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. METHODS: In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. RESULTS: The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. CONCLUSIONS: Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Treatment of an anterior communicating artery aneurysm through an anomalous anastomosis from the cavernous internal carotid artery.

Cavernous internal carotid artery (ICA)-anterior cerebral artery (ACA) anastomoses are unusual anomalies in which a duplicated A, segment of the ACA arises from the infraoptic ICA. The authors report on a 30-year-old woman who presented with subarachnoid hemorrhage from an anterior communicating artery (ACoA) aneurysm associated with an extremely rare variant of this anastomosis. The extra A, segment emerged from the ICA within the cavernous sinus rather than at or above the level of the ophthalmic artery. The presence of the anomalous vessel provided a straightforward endovascular approach to the ACoA and allowed the use of coil placement rather than surgical clipping to treat the aneurysm successfully.