Aggressive papillary glioneuronal tumor: case report and literature review.

Papillary glioneuronal tumors (PGNT) are a rare, recently described form of mixed neoplasm composed of glial and neuronal components. PGNT usually occur in children and young adults, and typically demonstrate low-grade pathology, with a low proliferative index of 1-3%. Here we describe a newly diagnosed case of PGNT with a more aggressive phenotype that required irradiation and chemotherapy. The patient was a 19-year-old female who developed progressive headaches and visual seizures. An MRI revealed a heterogeneously enhancing solid mass in the left temporo-occipital region, with significant surrounding edema and mass effect. The mass was resected under stealth guidance without complication. Postoperative MRI scans showed patchy enhancement and residual T2 and FLAIR abnormality. Pathology revealed a highly cellular neoplasm with papillary-like structures, containing cells with glial and neuronal differentiation. Regions of mitoses and focal necrosis were noted, along with a Ki-67 labeling index of 26%. The diagnosis was aggressive PGNT, and treatment consisted of conformal irradiation and concomitant temozolomide over 6 weeks. Postirradiation follow-up MRI scans demonstrated a reduction of residual enhancement and FLAIR abnormality. The patient continues standard-dose adjuvant temozolomide on a monthly basis, with further improvement on subsequent MRI scans and a stable neurologic exam. This patient demonstrates that PGNT may, in rare cases, display an aggressive clinicopathologic phenotype that requires a therapeutic approach more consistent with a high-grade glioma.

Neurological decompression illness and hematocrit: analysis of a consecutive series of 200 recreational scuba divers.

Neurological complications are common in recreational divers diagnosed with decompression illness (DCI). Prior reports suggest that hemoconcentration, with hematocrit values of 48 or greater, increase the risk for more severe and persistent neurological deficits in divers with DCI. Herein we describe our experience with neurological DCI and hematocrit values in a large series of consecutively treated divers. We performed a retrospective chart review of 200 consecutive recreational divers that received treatment for DCI. Standard statistical analyses were performed to determine if there were any significant relationships between diving-related or demographic parameters, neurological manifestations, and hematocrit. In 177 of the 200 divers (88.5%), at least one manifestation of neurological DCI (mild, moderate, or severe) was present. The median hematocrit value was 43, for both male and female divers, with a range of 30 to 61. Hematocrit values did not correlate with diver age or level of diving experience. In male divers, the hematocrit did not correlate with neurological symptoms, including the sub-group with values of 48 or greater. In contrast, female divers with hematocrit values of 48 or greater were significantly more likely to develop motor weakness (p=0.002, Fisher's exact test) and an increased number of severe sensory symptoms (p=0.001, Kendall's tau statistic). Neurological complications are common in recreational divers treated for DCI. Hematocrit values of 48 or higher were correlated with the presence of motor weakness and severity of sensory symptoms in female divers. The hematocrit did not correlate with neurological DCI in male divers.

Neurological manifestations of decompression illness in recreational divers - the Cozumel experience.

Neurological signs and symptoms are common in recreational divers with decompression illness (DCI). The spectrum of neurological manifestations, temporal profile, and laboratory findings are described in a large series of 200 consecutive recreational divers treated for DCI. The Hyperbaric Medicine Unit charts of 200 recreational divers treated for DCI were reviewed and analyzed. The cohort was mainly male, with a median age of 40 years, and quite experienced, with a median of 100 prior dives. In 44 divers (22%) a rapid ascent was documented. The median time to onset of neurological symptoms was 60 minutes after surfacing. One hundred seventy-seven of 200 divers (88.5%) had at least one symptom of neurological DCI at presentation. The most common neurological manifestations were paresthesia, dysesthesia, incoordination, motor weakness, and dizziness. Paresthesias were associated with significantly younger (p = 0.003) and less experienced (p = 0.03) divers. Similar but less significant correlations were noted for dysesthesias. Female divers were significantly more likely to experience painful skin symptoms (p < 0.001). Neurological manifestations are common in recreational divers treated for DCI. Neurological DCI and paresthesias are more likely to occur in younger and less experienced divers.

Prevalence and rupture rate of cerebral aneurysms discovered during intra-arterial chemotherapy of brain tumors.

BACKGROUND: During the administration of intra-arterial (IA) chemotherapy for the treatment of brain tumors (BTs), angiography may demonstrate asymptomatic, incidental cerebral aneurysms. The prevalence and complication rate of incidental aneurysms in patients undergoing IA chemotherapy remains unknown. It remains unclear whether the presence of an aneurysm represents an increased risk or a contraindication to this form of treatment. METHODS: We performed a chart and angiography review of BT patients receiving IA chemotherapy over the previous 16 months. Seventy-eight patients were identified with primary (39) and metastatic (39) BTs. RESULTS: The cohort consisted of 40 men and 38 women, with a mean age of 47.8 years (range, 22-80 years). During initial angiography, 8 patients (10.3%) were identified with incidental cerebral aneurysms. The aneurysms were saccular and varied in size from 2-4 mm (mean, 3 mm). Seven of the 8 patients continued IA chemotherapy after detection of the aneurysm, for a total of 35 IA procedures. Of these 7 patients, 5 expired from nonaneurysmal complications (mean survival, 5.4 months; range, 2-10 months); 4 from the primary tumor, and one from an infected craniotomy site. Two patients continue to survive; one remains in treatment, and the other has completed 12 months of IA therapy. There were no aneurysmal complications during or after IA treatment in any of the BT patients. CONCLUSION: Incidental aneurysms may be more common in patients with BTs than the general population. In our patient population, there was no indication that an incidental aneurysm was reason to preclude or delay the use of IA chemotherapy.

Weber's syndrome and sixth nerve palsy secondary to decompression illness: a case report.

We describe the first case of Weber's Syndrome to present as a manifestation of decompression illness in a recreational scuba diver. Weber's Syndrome is characterized by the presence of an oculomotor nerve palsy and contralateral hemiparesis. The patient was a 55 year-old male with a past medical history of a pulmonary cyst, in whom symptoms developed after a multilevel drift dive to a depth of 89 feet for 53 minutes, exceeding no-decompression limits. Symptom onset was within 30 minutes of surfacing and included the Weber's Syndrome, a sixth nerve palsy, dizziness, nausea, sensory loss, and ataxia. The patient received four U.S. Navy Treatment Tables with complete resolution of all neurological signs and symptoms. The mechanism of injury remains unclear, but may involve aspects of both air gas embolism and decompression sickness. Individuals with pre-existing pulmonary cysts may be at increased risk for dive-related complications.

Glucosephosphate isomerase as a CSF marker for leptomeningeal metastasis.

Glucosephosphate isomerase (GPI), also known as phosphohexoisomerase, is a glycolytic enzyme whose activity is elevated in serum and CSF of patients with primary and metastatic CNS tumors. To improve the diagnostic accuracy of leptomeningeal metastasis (LM), we measured GPI levels in CSF of 66 patients with CNS or systemic malignancies with suspected LM. We determined GPI kinetically using a coupled enzyme reaction assay. There were 31 males and 35 females, aged 1 to seventy-six. Thirty-one had primary brain tumors, and 35 had systemic cancer with suspected CNS metastasis. We analyzed 95 samples; GPI values ranged from 0.85 to 329.0 U/l (normal, less than 20 U/l). Compared with positive CSF cytology and myelography, GPI sensitivity was 53.5% and specificity 92.1% for the group as a whole. There was a highly significant association between elevated CSF GPI (greater than 20 U/l) and LM. The results were similar for both primary CNS and systemic malignancies. Although not very sensitive, an elevated CSF GPI strongly suggests LM and may aid in early diagnosis of this serious complication of cancer.

Swallowing assessment in primary brain tumor patients with dysphagia.

Dysphagia is a common problem in patients with neurologic disease and is often associated with significant morbidity and mortality. To evaluate primary brain tumor patients who complained of dysphagia, we adapted grading scales for severity of complaint and level of alertness (scale of 1 to 4) and bedside swallowing assessment and videofluoroscopic examination (scales of 1 to 5). Over 13 months, we prospectively screened 117 patients for dysphagia. Seventeen of these (14.5%) complained of dysphagia (mean age, 50.2 years; range, 20 to 75); an additional six control patients were studied from a group with no dysphagic complaints. Scoring for severity of complaint (mean, 2.3) and level of alertness (mean, 2.2) was mild-moderate in the majority of patients. Eleven of 17 patients scored > or = grade 3 (mean 3.2, moderate impairment, requiring supervision) on bedside testing, and six of seven scored > or = grade 3 (mean 3.8, moderate-moderately severe abnormality, trace or frequent aspiration) during videofluoroscopic evaluation. Bedside testing scores of the study group differed significantly (p < 0.001) from those of the control group. Level of alertness correlated strongly with bedside (r = 0.794) and videofluoroscopic (r = 0.780) scoring. Primary brain tumor patients with dysphagia are likely to have impairment of swallowing out of proportion to their complaints and therefore are at risk for aspiration and nutritional compromise. We recommend that these patients undergo formal swallowing assessment followed by rehabilitation or implementation of alternative feeding methods.

Procarbazine chemotherapy in the treatment of recurrent malignant astrocytomas after radiation and nitrosourea failure.

The Brain Tumor Study Group has shown procarbazine (PCB) to be as effective an adjuvant treatment as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We treated 35 patients with recurrent malignant astrocytomas after radiation and nitrosourea failure with successive courses of PCB 150 mg/m2/d for 28 days every 8 weeks. After 2 courses, 2 patients had complete responses, 7 had partial responses, 11 had stable disease, and 15 had progression. Significantly more patients receiving PCB had complete or partial responses or stable disease than a similar group of patients in a previous trial who received intra-arterial (IA) cisplatin (DDP). There is a significant advantage in time to disease progression for those receiving PCB compared with those receiving IA diaziquone (AZQ). Our results suggest that PCB is a more effective 2nd agent than IA DDP or AZQ following radiation and nitrosourea failure.

Novel chemotherapeutic agents for the treatment of brain cancer.

Brain cancer encompasses both primary and metastatic brain tumours and accounts for over 120,000 new patients each year. Despite aggressive therapy, the majority of patients with brain cancer have poor prognosis and have brief survival intervals. Current chemotherapy drugs, used alone or in combination, have minimal or only modest activity. Novel agents that have recently been applied to brain cancer include temozolomide, irinotecan and paclitaxel. Temozolomide is a DNA alkylating agent, irinotecan inhibits DNA topoisomerase I and paclitaxel binds to microtubules and induces polymerisation. Neoplastic angiogenesis and brain tumour invasion are also targets for therapeutic intervention with new agents such as thalidomide, suramin and marimastat. All of these agents have demonstrated activity against brain cancer in vitro. Several of the drugs, in particular temozolomide, paclitaxel and irinotecan, have entered preliminary clinical trials and have demonstrated some efficacy. However, chemotherapy for primary brain tumours remains rather non-specific and mostly ineffective. The use of chemotherapy may be more effective against selected metastatic brain tumours. Continued basic research is needed to further elucidate the genetic basis of transformation, tumour invasion and angiogenesis. It is hoped that this research will lead to new therapeutic targets for drug design and development. In addition, new strategies must be developed to overcome the problem of chemotherapy resistance.

Review of the molecular genetics and chemotherapeutic treatment of adult and paediatric medulloblastoma.

Medulloblastoma is the most common primary brain tumour in children and accounts for 25% of newly diagnosed cases. Recent advances in treatment have extended 5-year survival rates from 3 - > 70% during the past 50 years. These improvements in survival have resulted from a multi-modality approach that includes surgical resection, posterior fossa and craniospinal irradiation and chemotherapy for selected, high-risk patients. The literature regarding chemotherapy of adult and paediatric patients is reviewed in-depth. The most active agents include cisplatin, CCNU, cyclophosphamide, vincristine and carboplatin. Although patients are living longer with their disease, neurocognitive function and quality of life are often impaired following radiation therapy (RT) to the developing brain. To safely allow reductions in the dose of RT, the specificity and efficacy of chemotherapy must be improved. Recent advances in the molecular genetics of medulloblastoma transformation (e.g., myc, PTCH ) are reviewed and discussed. A thorough understanding of these pathways will be critical for the development of more specific, novel drugs. Further clinical trials will be needed to evaluate the activity of these new drugs and determine their role in the treatment plan of patients with medulloblastoma.

"One-and-a-half" syndrome after a resection of a midline cerebellar astrocytoma: case report and discussion of the literature.

This report describes a rare complication after the resection of a tumor of the posterior fossa, the "one-and-a-half" syndrome. The one-and-a-half syndrome is a disturbance of horizontal eye movements in which patients have lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other direction. The patient was a 54-year-old woman who developed headaches, diplopia, and blurred vision over 6 months. Computed tomographic scans and magnetic resonance imaging demonstrated an enhancing, mixed density, midline mass of the cerebellum. After a resection of the mass, an anaplastic astrocytoma, the patient complained of more severe diplopia and facial weakness. An examination disclosed a left one-and-a-half syndrome, left peripheral facial paralysis, dysarthria, dysphagia, mild left hemiparesis, dysmetria of the left upper limb, and truncal ataxia. The brain stem showed no abnormalities on postoperative computed tomographic scans. After 4 months of follow-up, the one-and-a-half syndrome had not improved, even though other signs had improved or resolved. This syndrome is caused by damage to structures within the pontine tegmentum: the medial longitudinal fasciculus, the ipsilateral paramedian pontine reticular formation, or the ipsilateral abducens nucleus. Multiple sclerosis and brain stem infarction are the most common causes of the one-and-a-half syndrome. Less frequently, it is caused by primary and metastatic tumors of the brain stem and cerebellum. Rarely, the one-and-a-half syndrome can develop postoperatively after the removal of tumors of the posterior fossa. The mechanism of pontine tegmental injury remains unknown.

Extracranial plasma cell granuloma presenting as a diffuse meningeal and intraparenchymal mass.

Plasma cell granuloma (PCG) is uncommon, characterized by polyclonal proliferation of mature plasma cells, usually within systemic organs. Only four previous cases have involved the central nervous system (CNS).

Progressive multifocal leukoencephalopathy presenting as multiple enhancing lesions on MRI: case report and literature review.

This report describes an immunocompetent patient with memory loss and motor abnormalities whose magnetic resonance images demonstrated multiple enhancing white matter lesions, including one that was cystic, suggestive of metastatic tumors or abscesses. Neuropathological evaluation at biopsy and subsequent autopsy revealed progressive multifocal leukoencephalopathy. Magnetic resonance evidence of enhancement and cystic changes are rare findings in progressive multifocal leukoencephalopathy, but should be considered in the differential diagnosis, especially in patients without evidence for primary malignancy or infection.

MicroRNAs and glioblastoma; the stem cell connection.

Recent data draw close parallels between cancer, including glial brain tumors, and the biology of stem and progenitor cells. At the same time, it has become clear that one of the major roles that microRNAs play is in the regulation of stem cell biology, differentiation, and cell 'identity'. For example, microRNAs have been increasingly implicated in the regulation of neural differentiation. Interestingly, initial studies in the incurable brain tumor glioblastoma multiforme strongly suggest that microRNAs involved in neural development play a role in this disease. This encourages the idea that certain miRs allow continued tumor growth through the suppression of differentiation and the maintenance of the stem cell-like properties of tumor cells. These concepts will be explored in this article.

Common neurologic complications of HIV-1 infection and AIDS.

Complications of human immunodeficiency virus type 1 infection and acquired immunodeficiency syndrome may involve any level of the central or peripheral nervous system. Acute encephalitis, aseptic meningitis and acute demyelinating polyneuropathy may occur early in the course of HIV infection, while dementia, central nervous system-related cancer, opportunistic infections and autonomic neuropathy typically present later. Headache and mental status changes are common early manifestations of central nervous system involvement. Most severe headaches are related to an identifiable cause, including a mass lesion, opportunistic cerebral infection and medication side effect. Memory deficits, concentration difficulties and abnormalities on mental status testing may represent early AIDS dementia complex (HIV encephalopathy), the most common neurologic complication. In patients with AIDs, the differential diagnosis of cerebral mass lesions on computed tomography or magnetic resonance imaging includes cerebral toxoplasmosis, tuberculous or fungal abscess, focal viral encephalitis, metastatic resonance imaging includes cerebral toxoplasmosis, tuberculous or fungal abscess, focal viral encephalitis, metastatic Kaposi's sarcoma and primary CNS lymphoma. Peripheral neuromuscular disease, including distal symmetric polyneuropathy, autonomic neuropathy, and HIV and chronic zidovudine myopathy, affects 15 to 40 percent of all persons with HIV infection or AIDS.

Primary brain tumors: review of etiology, diagnosis and treatment.

The activation of oncogenes and the inactivation of tumor suppressor genes within neoplastic cells lead to transformation and loss of growth control. The key clinical feature that should arouse suspicion of a primary brain tumor and lead to a prompt evaluation is the progressive nature of the signs and symptoms, which include headaches, nausea and emesis, double vision, change in personality or cognition, speech difficulty, seizures and weakness. Neuroimaging with contrast-enhanced computed tomography or magnetic resonance imaging is the best method of confirming the presence of a primary brain tumor. Initial treatment in most patients is biopsy or surgical resection. For malignant and selected benign primary brain tumors, further treatment is necessary and may include radiation therapy, chemotherapy or experimental protocols.

Neurologic complications of systemic cancer.

Neurologic complications occur frequently in patients with cancer. After routine chemotherapy, these complications are the most common reason for hospitalization of these patients. Brain metastases are the most prevalent complication, affecting 20 to 40 percent of cancer patients and typically presenting as headache, altered mental status or focal weakness. Other common metastatic complications are epidural spinal cord compression and leptomeningeal metastases. Cord compression can be a medical emergency, and the rapid institution of high-dose corticosteroid therapy, radiation therapy or surgical decompression is often necessary to preserve neurologic function. Leptomeningeal metastases should be suspected when a patient presents with neurologic dysfunction in more than one site. Metabolic encephalopathy is the common nonmetastatic cause of altered mental status in cancer patients. Cerebrovascular complications such as stroke or hemorrhage can occur in a variety of tumor-related conditions, including direct invasion, coagulation disorders, chemotherapy side effects and nonbacterial thrombotic endocarditis. Radiation therapy is the most commonly employed palliative measure for metastases. Chemotherapy or surgical removal of tumors is used in selected patients.

Neurologic complications of scuba diving.

Recreational scuba diving has become a popular sport in the United States, with almost 9 million certified divers. When severe diving injury occurs, the nervous system is frequently involved. In dive-related barotrauma, compressed or expanding gas within the ears, sinuses and lungs causes various forms of neurologic injury. Otic barotrauma often induces pain, vertigo and hearing loss. In pulmonary barotrauma of ascent, lung damage can precipitate arterial gas embolism, causing blockage of cerebral blood vessels and alterations of consciousness, seizures and focal neurologic deficits. In patients with decompression sickness, the vestibular system, spinal cord and brain are affected by the formation of nitrogen bubbles. Common signs and symptoms include vertigo, thoracic myelopathy with leg weakness, confusion, headache and hemiparesis. Other diving-related neurologic complications include headache and oxygen toxicity.

Attempted dose intensified cyclophosphamide, etoposide, and granulocyte colony-stimulating factor for treatment of malignant astrocytoma.

Patients with malignant astrocytoma continue to respond poorly to chemotherapy and have a dismal prognosis. Cyclophosphamide (CTX) and etoposide demonstrate activity against malignant astrocytoma at standard dosages, with bone marrow suppression as the limiting toxicity. In order to allow dose intensification, minimize leukopenia, and improve efficacy granulocyte colony-stimulating factor (G-CSF) was used in combination with CTX and etoposide. The protocol consisted of CTX (2 mg/m2/d, days 1, 2), etoposide (200-300 mg/m2/d, days 1-3), and G-CSF (5-10 micrograms/d subcutaneously, days 4-18), every 4 weeks. Nine evaluable patients (7 glioblastoma multiforme, 2 anaplastic astrocytoma) were treated, ranging in age from 26-67 (mean 41). One of 9 patients responded (11%) with a partial response (13+ months), 3 had stable disease (33%; 8, 5, 2.5 months), and 5 had progressive disease (3, 2.5, 2, 1.5, 1 months). The median time to progression for responders was 6.5 months, while overall it was 2.5 months. Overall median survival was only 7.0 months. Toxicity was frequent and severe, typically delaying treatment cycles. The most common complications were severe myeolosuppression (9), sepsis (8), rash (6), urinary infection (5), and anorexia (5). Treatment delays caused by infections and other complications occurred often, abrogating the intended dose intensification. The received dose intensity (DI) for CTX was 400-425 mg/m2/week (relative DI 0.41), while for etoposide it was 75 mg/m2/week (relative DI 0.42). In summary, as used in this protocol, dose intensive chemotherapy with CTX, etoposide, and G-CSF does not improve efficacy over standard regimens and results in excessive toxicity.

Lhermitte's sign as a presenting symptom of primary spinal cord tumor.

We describe a previously healthy 29 year-old man who developed Lhermitte's sign, a shock-like or electric sensation, transmitted down the spine, which occurred during neck flexion or rotation. Evaluation demonstrated an intrinsic, fusiform mass extending from c5 to c7. At operation, the mass was completely removed and found to be a low-grade ependymoma. The sensory phenomena of Lhermitte's sign were most likely caused by tumor-induced distortion and demyelination of cervical dorsal column sensory axons. Lhermitte's sign is most prevalent in patients with multiple sclerosis, cervical spondylotic myelopathy, cisplatin neurotoxicity, cervical radiation injury, and neck trauma. Rarely, Lhermitte's sign occurs with spinal cord compression from epidural or subdural tumor. This patients is the first reported case of an intrinsic spinal cord tumor to present with Lhermitte's sign.