Human immunodeficiency virus encephalitis causes
Granular cell astrocytomas (GCAs) are rare, incompletely characterized infiltrative gliomas that contain a prominent component of granular cells. Such tumors can readily be mistaken for reactive conditions. We studied 22 cases to explore their morphologic spectrum, establish features useful in distinguishing GCA from nonneoplastic diseases, and to determine which parameters correlate with biologic behavior. Tumors occurred in 17 men and five women, ranging in age from 29 to 75 years, who presented mainly with seizures, headache, aphasia, or hemiparesis. Radiologically, high-grade GCAs were contrast-enhancing, cerebral hemispheric masses with prominent peritumoral edema. All contained sheets or interspersed large, round cells packed with eosinophilic, PAS-positive granules. Lymphocytic infiltrates, either perivascular or admixed with neoplastic cells, were present in 14 tumors. Transition to typical infiltrating astrocytoma was noted in 16 cases; of these, granular cells comprised 30-95% of cells. Six tumors consisted almost entirely of atypical granular cells. By WHO criteria, four GCA were grade 2, seven were grade 3, and 11 were grade 4. Glial fibrillary acidic protein staining was seen in all but one tumor, and the majority were immunoreactive for S-100 protein, KP-1, ubiquitin, and epithelial membrane antigen. Although MIB-1 proliferation indices increased with tumor grade, granular cells accounted for only a minority of immunoreactive cells. Among 18 cases with follow-up, 15 recurred after surgery and resulted in death (mean survival, 7.6 months). Two patients died postoperatively, and one was alive at 51 months. Granular cell astrocytoma is an uncommon morphologic variant that appears to be rapidly progressive and usually fatal.
Telepathology is an attractive solution for providing neuropathologic intraoperative expertise to geographically diverse hospitals from a center of excellence. To date, few reports specifically address the feasibility of such a system for intraoperative neuropathology specimens. The University of Pittsburgh Medical Center is a 20-hospital system in Southwest Pennsylvania in which the pathology department has adopted a subspecialty "centers of excellence" method of managing cases. The Division of Neuropathology is physically located at 1 hospital but provides neuropathologic expertise to the entire system. Adult neurosurgery is currently limited to 2 hospitals separated by 18 city blocks. We describe our experience in providing remote intraoperative neuropathologic consultations over a 5-year period, from 2002 to 2006. Several approaches are discussed, with emphasis on the current system and the evolution of imaging technology. Diagnostic outcomes are compared among >400 telepathology cases and >1,200 conventional intraoperative cases. Current technology is capable of facilitating teleneuropathologic intraoperative diagnoses in a timely manner, with accuracy rates comparable to those for conventional methods. However, the practice of providing these remote consultations requires a sophisticated and technologically advanced environment along with substantial planning, communication, and training of both pathologists and pathology assistants.
In pheochromocytoma (PC12) cells nerve growth factor (NGF) and epidermal growth factor (EGF) activate similar receptor tyrosine kinase signaling pathways but evoke strikingly different biological outcomes: NGF induces differentiation and EGF acts as a mitogen. A novel approach was developed for identifying transcription factor activities associated with NGF-activated, but not EGF-activated, signaling, using random oligonucleotide clones from a DNA recognition library to isolate specific DNA binding proteins from PC12 nuclear extracts. A protein complex from NGF-treated, but not EGF-treated, cells was identified that exhibits increased mobility and DNA binding activity in gel mobility shift assays. The binding complex was identified in supershift assays as Fra-2/JunD. The clones used as probes contain either AP-1 or cAMP response element binding (CREB) recognition elements. Time course experiments revealed further differences in NGF and EGF signaling in PC12 cells. NGF elicits a more delayed and sustained ERK phosphorylation than EGF, consistent with previous reports. Both growth factors transiently induce c-fos, but NGF evokes a greater response than EGF. NGF specifically increases Fra-1 and Fra-2 levels at 4 and 24 hr. The latter is represented in Western blots by bands in the 40-46 kDa range. NGF, but not EGF, enhances the upper bands, corresponding to phosphorylated Fra-2. These findings suggest that prolonged alterations in Fra-2 and subsequent increases in Fra-2/JunD binding to AP-1 and CREB response elements common among many gene promoters could serve to trigger broadly an NGF-specific program of gene expression.
Background The efficacy of temozolomide (TMZ) chemotherapy for treating newly diagnosed glioblastoma (GBM), a primary brain tumor with short survival, was demonstrated in a clinical trial in 2005, and since then, the standard-of-care for newly diagnosed GBM has been maximal safe surgery followed by 60 Gray of radiation with concomitant and adjuvant TMZ (standard radiotherapy and TMZ). In 2009, clinical trials also reported on the efficacy of bevacizumab for treating recurrent GBM. We performed a retrospective cohort study to evaluate the impact of treatment regimens on overall survival for patients with GBM at a rural tertiary healthcare practice. Methods We retrospectively reviewed the medical records of 307 consecutive, newly diagnosed GBM patients at one institution between 1995 and 2012 and assessed treatment patterns. We also compared overall survival according to the treatment received. Results Only 0.6% (1/163) of patients diagnosed before 2005 received standard radiotherapy and TMZ versus 36.1% (52/144) of patients diagnosed since 2005 (P < 0.0001). For patients who received standard radiotherapy and TMZ, the median overall survival was 17.0 months versus 7.0 months for patients who received 60 Gray of radiation but no chemotherapy (P = 0.0000078). The median overall survival was 15.4 months in the 19 patients treated with bevacizumab monotherapy at first GBM recurrence versus 6.8 months in the 32 patients with no treatment at first GBM recurrence (P = 0.00015), but patients who received bevacizumab were younger and more likely to have had a surgical resection and 60 Gray of radiation at diagnosis. Conclusions TMZ and bevacizumab therapies were rapidly adopted in a rural tertiary healthcare setting, and patients who received these treatments had increased overall survival. However, advantageous prognostic factors in patients who received bevacizumab at recurrence may have influenced the extent of the increase in overall survival attributed to this treatment.
A male patient, aged 55 years, presented to the emergency room with complaints of bilateral upper extremity weakness. His past medical history was significant for paraplegia and neurogenic bladder from a spinal cord injury, complicated with decubitus ulcers and end-stage renal disease secondary to type II diabetes mellitus. His past surgical history was significant for posterior spine fusion with Harrington rod instrumentation at the level of T10. He developed subacute onset of bilateral upper extremity weakness and paresthesias on the day of presentation. He reported a 2-day history of neck and back pain that he initially contributed to his bedridden state. The patient denied fever, recent infections, or trauma. His vital signs were unremarkable. Physical examination revealed quadriparesis, absence of deep tendon reflexes, hypoesthesia, and decubitus ulcers (figure 1). He had a normal leukocyte count and elevated C-reactive protein. Blood cultures and cultures from the ulcers were obtained. With the concern of spinal cord compression based on presentation, intravenous corticosteroids and broad spectrum antibiotics were initiated. A magnetic resonance imaging (MRI) scan of the spine (figure 2) revealed large elongated epidural collection posteriorly within the cervical spine, extending into the thoracic spine and inferiorly. Spinal cord compression was prominent in the narrowed areas of disc-osteophyte complexes at the levels of C3-4 and C5-6, where the spinal cord was compressed between these disc-osteophyte complexes and the posterior epidural collection, with some mildly increased signal intensity within the cord. The lumbosacral spine was not well imaged due to artifacts of spinal hardware. Emergent drainage of the collection was indicated, but the patient declined. Per the patient's wishes, palliative care was initiated on the day Spinal subdural abscess (SSA) is an uncommon entity. The exact incidence is unknown, with very few cases reported in the literature. This condition may result in spinal cord compression, thus constituting a medical and neurosurgical emergency. The pathogenesis of SSA is not welldescribed, and the available knowledge is based on case observations only. There is only one case report that describes direct seeding from decubitus ulcers as a possible mechanism for development of SSA. We report a case of subacute onset of quadriplegia in a male patient, age 55 years, due to spinal cord compression from SSA and superimposed spinal subdural hematoma. The direct seeding from decubitus ulcers is thought to be the cause of infection in our patient. We present this case of SSA to elucidate and review the predisposing factors, pathogenesis, clinical presentation, diagnostic modalities, and treatment regarding management of this rare disorder.
Since its description in 1982, central neurocytoma (CN) has been a relatively innocuous rare tumor of the central nervous system. Comprising of less than 0.5% of all intracranial tumors, most are reported to be slow growing, with low recurrence rates, and a favorable prognosis. Because of its rarity, its cellular biology, prognosis, and treatment strategies are difficult to ascertain. Its low-grade nature allows for continued growth before signs and symptoms of increase intracranial pressures ensue. Some authors theorize CN may derive from bipotential precursor cells of the periventricular germinal matrix, which are capable of both neuronal and glial differentiation, but maintain a low proliferative potential after birth. Several retrospective studies indicate that a MIB-1 index of greater than 2-3% will show a recurrence rate of 48-63%, respectively. Of hundreds of cases reported, the incidence of recurrence is very low, which makes aggressive forms of this tumor difficult to study. There are only 12 cases of craniospinal dissemination reported since its inception. The diagnoses of dissemination in these cases are made only after surgical intervention. We report the only case of primary disseminated CN, diagnosed on radiographic studies, and confirmed by cytology of the cerebral spinal fluid, prior to any kind of intervention. These cases may represent a subgroup of a more aggressive CN, which requires more assertive surveillance including CSF sampling and routine imaging of the neuroaxis.
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