Leptomeningeal melanocytosis in an adult male without large congenital nevi: a rare and atypical case of neurocutaneous melanosis.

Leptomeningeal melanocytosis is a primary melanocytic lesion of the central nervous system that is characterized by diffuse melanocytic infiltration of the leptomeninges. It is seen almost exclusively in children with large congenital nevi and together the findings form a dermatologic syndrome known as neurocutaneous melanosis. We report a rare and atypical case of a 31-year-old adult male with no evident congenital melanocytic lesions who presented with neurologic symptoms and was found to have leptomeningeal melanocytosis. The brain biopsy demonstrated a conspicuous but benign-appearing melanocytic infiltrate that was discordant with the severity of the patient's symptoms. Ultimately, the patient was suspected to represent a case of former fruste neurocutaneous melanosis. Herein the relevant clinical and histopathologic features are discussed along with a brief review of the literature.

Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta 2-interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts.

We have defined the expression of the mRNA for, and secretion of, IFN-beta 2/hepatocyte-stimulating factor/IL-6 (IFN-beta 2/IL-6) in human diploid fibroblasts (FS-4 strain) infected with different RNA- and DNA-containing viruses. RNA blot-hybridization analyses carried out 6-8 h after the beginning of infection showed that the RNA-containing Sendai virus (paramyxoviridae) enhanced IFN-beta 2/IL-6 mRNA levels 10-fold, followed, in decreasing order, by encephalomyocarditis (EMC, picornaviridae), vesicular stomatitis (VSV, rhabdoviridae), Newcastle disease virus (NDV, paramyxoviridae), and influenza A (Flu, myxoviridae) viruses. The DNA-containing pseudorabies virus (PR, herpesviridae) enhanced IFN-beta 2/IL-6 mRNA levels sixfold, while the effect of adenovirus type 5 (Ad5, adenoviridae) was considerably less and comparable with that of NDV or Flu. A rabbit antiserum raised against E. coli-derived human IFN-beta 2/IL-6 was used in immunoprecipitation experiments to monitor the secretion of 35S-methionine-pulse-labeled IFN-beta 2/IL-6 proteins by fibroblasts up to 7 h after the beginning of infection. Enhanced levels of secretion of IFN-beta 2/IL-6 (2-14-fold) were observed in every instance evaluated (Sendai, EMC, VSV, Flu, PR, Ad5 viruses). A biological consequence of enhanced secretion of IFN-beta 2/IL-6 was the ability of media from infected FS-4 cell cultures to enhance by 8-15-fold the synthesis and secretion of a typical acute phase plasma protein (alpha 1-antichymotrypsin) by human hepatoma Hep3B2 cells. These observations make it likely that IFN-beta 2/IL-6 mediates, in part, the host response to acute virus infections.

Neurosurgical management of low- and intermediate-grade gliomas.

Surgery remains an effective treatment for most histologic types of low- and intermediate-grade gliomas and is an important part of their initial management. Controversies nonetheless abound regarding the timing and goals of surgery for these gliomas. This article reviews surgical therapy of low- and intermediate-grade gliomas, paying special attention to new surgical techniques.

Selective putaminal excitotoxic lesions in non-human primates model the movement disorder of Huntington disease.

While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease.

Effects of striatal excitotoxicity on huntingtin-like immunoreactivity.

The relationship between the specific neuronal loss observed in Huntington's disease and the mutation in the IT15 gene responsible for this disease remains obscure. Using an antipeptide antibody against amino acids 3114-3141 of the human huntington protein, we demonstrate that striatal injection of quinolinic acid in mice induces increased immunoreactivity for huntington in some remaining neurons but not in glial cells. This increase is apparent in both neuronal cell bodies and in cell processes in the white matter six hours after excitotoxic challenge. This finding suggests that huntington may be involved in the response to excitotoxic stress in these neurons.

Cell-mediated delivery of brain-derived neurotrophic factor enhances dopamine levels in an MPP+ rat model of substantia nigra degeneration.

Brain-derived neurotrophic factor (BDNF) promotes the survival of fetal mesencephalic dopaminergic cells and protects dopaminergic neurons against the toxicity of MPP+ in vitro. Supranigral implantation of fibroblasts genetically engineered to secrete BDNF attenuates the loss of substantia nigra pars compacta (SNc) dopaminergic neurons associated with striatal infusion of MPP+ in the adult rat. Using this MPP+ rat model of nigral degeneration, we evaluated the neurochemical effects of supranigral, cell-mediated delivery of BDNF on substantia nigra (SN) dopamine (DA) content and turnover. Genetically engineered BDNF-secreting fibroblasts (approximately 12 ng BDNF/24 h) were implanted dorsal to the SN 7 days prior to striatal MPP+ administration. The present results demonstrate that BDNF-secreting fibroblasts, as compared to control fibroblasts, enhance SN DA levels ipsilateral as well as contralateral to the graft without altering DA turnover. This augmentation of DA levels suggests that local neurotrophic factor delivery by genetically engineered cells may provide a therapeutic strategy for preventing neuronal death or enhancing neuronal function in neurodegenerative diseases characterized by dopaminergic neuronal dysfunction, such as Parkinson's disease.

Flow-directed atrial catheter placement for ventriculoatrial shunts: technical note.

The placement of the atrial portion of a ventriculoatrial shunt is occasionally rendered difficult by a tendency of the shunt catheter to pass into the contralateral jugular vein or into a subclavian vein instead of into the atrium. We report a simple flow-directed technique that may resolve this problem.

Aneurysmal and microaneurysmal "angiogram-negative" subarachnoid hemorrhage.

The source of bleeding remains obscure in most cases of subarachnoid hemorrhage (SAH) with a negative angiogram. From January 1, 1989, to July 1, 1993, 40 patients were admitted to the Massachusetts General Hospital with angiogram-negative SAH; 9 of these patients underwent surgical exploration. In seven of these explorations, an arterial source of the hemorrhage was discovered. These arterial sources included three anterior communicating artery complex lesions, two middle cerebral artery lesions, one internal carotid artery aneurysm arising at the origin of the posterior communicating artery, and one vertebral/posterior inferior cerebellar artery aneurysm. Three of these seven lesions had small aneurysmal sacs, but the other four were microaneurysms too small to accept a surgical clip. No source of hemorrhage could be found during surgery on one patient with a perimesencephalic pattern of blood. Two of the four patients with a microaneurysmal source of hemorrhage had two episodes of SAH. We propose that microaneurysms are the source of a significant percentage of nonperimesencephalic angiogram-negative SAH and suggest that these lesions may represent a forme fruste of saccular aneurysms. These findings lead us to propose a protocol for the management of angiogram-negative SAH based on the distribution of blood as seen on the patient's first computed tomogram.

Hemorrhage into a lumbar synovial cyst causing an acute cauda equina syndrome. Case report.

Juxtafacet cysts of the lumbar spine have been reported with increasing frequency but their pathogenesis remains obscure. These cysts most frequently present with back pain, followed by chronic progressive radiculopathy or gradual onset of symptoms of spinal canal compromise. The authors report an unusual case of hemorrhage into a right L3-4 synovial cyst causing an acute cauda equina syndrome and describe its successful surgical treatment. The clinical, radiographic, and pathological features are discussed.

Central neurocytomas of the cervical spinal cord. Report of two cases.

Central neurocytoma is a neuronal neoplasm that occurs supratentorially in the lateral or third ventricles. The authors report the clinical, neuroradiological, and neuropathological features of two neurocytomas arising in the spinal cord of two men, aged 65 and 49 years. The patients presented with progressive neurological deficits referable to the cervical spinal cord. Magnetic resonance imaging revealed isodense intramedullary spinal cord tumors at the C3-4 level. Both tumors were initially misdiagnosed as gliomas. In Case 1 the correct diagnosis was made after electron microscopy revealed neuronal features. Immunostaining in Case 2 revealed that tumor cells were positive for synaptophysin and negative for glial fibrillary acidic protein, strongly indicating a neuronal tumor. It is suggested that this spinal cord neoplasm be included under the designation "central neurocytoma."

Third ventricular xanthogranulomas clinically and radiologically mimicking colloid cysts. Report of two cases.

Two cases are reported of third ventricle masses that were clinically and radiographically indistinguishable from pure colloid cysts. A 21- and a 36-year-old man presented with a 5-year and 10-day histories of headache, respectively. Magnetic resonance (MR) imaging revealed smooth, homogeneous masses in the anterior third ventricle that were iso- to hyperintense on T1-weighted MR images and hyperintense on T2-weighted images. There was little enhancement with intravenous contrast material. In both patients, craniotomies were performed and histopathological examination revealed xanthogranulomas of the choroid plexus with only microscopic foci of colloid cyst-like structures. These cases illustrate that xanthogranulomas of the third ventricle may clinically and radiologically mimic pure colloid cysts, that a range of MR imaging signals can be seen, and that craniotomy rather than stereotactic aspiration is the indicated treatment.

Neurosurgical management of brain tumors.

The combination of surgery and radiation remains the most effective treatment for tumors affecting the central nervous system. This article reviews surgical therapy for brain tumors. Special attention is paid to new approaches to brain tumor therapy and to the interaction between neuroimaging and successful surgery.

Fatal intracerebral hemorrhage following thrombolytic therapy of embolic myocardial infarction in unsuspected infective endocarditis.

Cerebral hemorrhage occurs in 0.2% of patients under the age of 60 years treated with thrombolytic therapy for acute myocardial infarction. A case of fatal cerebral hemorrhage following TPA therapy for myocardial infarction due to probable coronary artery embolism during unsuspected native valve infective endocarditis is reported.

Does MR perfusion imaging impact management decisions for patients with brain tumors? A prospective study.

BACKGROUND AND PURPOSE: MR perfusion imaging can be used to help predict glial tumor grade and disease progression. Our purpose was to evaluate whether perfusion imaging has a diagnostic or therapeutic impact on clinical management planning in patients with glioma. MATERIALS AND METHODS: Standard MR imaging protocols were interpreted by a group of 3 NRs in consensus, with each case being interpreted twice: first, including routine sequences; and second, with the addition of perfusion imaging. A multidisciplinary team of treating physicians assessed tumor status and created hypothetical management plans, on the basis of clinical presentation and routine MR imaging and then routine MR imaging plus perfusion MR imaging. Physicians' confidence in the tumor status assessment and management plan was measured by using Likert-type items. RESULTS: Fifty-nine consecutive subjects with glial tumors were evaluated; 50 had known pathologic diagnoses. NRs and the treatment team agreed on tumor status in 45/50 cases (κ = 0.81). With the addition of perfusion, confidence in status assessment increased in 20 (40%) for NRs and in 28 (56%) for the treatment team. Of the 59 patient-care episodes, the addition of perfusion was associated with a change in management plan in 5 (8.5%) and an increase in the treatment team's confidence in their management plan in 34 (57.6%). NRs and the treatment team found perfusion useful in most episodes of care and wanted perfusion included in future MR images for >80% of these subjects. CONCLUSIONS: Perfusion imaging appears to have a significant impact on clinical decision-making and subspecialist physicians' confidence in management plans for patients with brain tumor.

Acute lacunar stroke in association with angiogram-negative subarachnoid hemorrhage. Mechanistic implications of two cases.

BACKGROUND AND PURPOSE: Although there is much speculation regarding the source of bleeding in patients with subarachnoid hemorrhage when no angiographic abnormality is found, little direct evidence has been obtained to document a cause. We report two cases of stroke in the distribution of a perforating or lenticulostriate artery occurring at the time of angiogram-negative subarachnoid hemorrhage. CASE DESCRIPTIONS: A 68- and a 60-year-old man each presented with acute onset of headache and meningismus. Computed tomography (CT) revealed subarachnoid hemorrhage in a perimesencephalic pattern and in the left sylvian fissure, respectively. In both instances, immediate CT revealed evidence of an early infarction in the distribution of a perforating artery originating at the site of the subarachnoid blood. Both of these strokes were demonstrated to be acute by evolution on serial imaging studies. No source for the subarachnoid blood could be found in either patient in cerebral angiograms repeated at 2 weeks. CONCLUSIONS: These observations suggest that in some cases of angiogram-negative subarachnoid hemorrhage the source of blood may be a small artery that is obliterated at the time of hemorrhage. This observation provides an explanation for the low rate of rehemorrhage among patients with angiogram-negative subarachnoid hemorrhage.