Intracranial pial arteriovenous fistula in infancy: a case report and literature review.

Intracranial pial arteriovenous fistulas (AVF) are rare vascular malformation especially in the first 2 years of life. The pathology in this age group is associated with greater morbidity and mortality. We report a rare case of 36-day-old male infant with a pial AVF associated with an arterial aneurysm, who presented with intraventricular hemorrhage and hydrocephalus. In addition, an online review of the literatures on pediatric pial AVF was performed using PubMed on published case reports and articles from 1980 to April 2013.

Lethal intratumoral haemorrhages of brain metastases during radiosurgery: case reports and literature review.

Gamma Knife surgery (GKS) is an effective and important treatment modality in the management of brain metastases. The short-term complication rate is low and the tumour control rate high. Complications caused by acute radiation-induced oedema are rare and usually benign. In this article, two cases of lethal haemorrhagic event immediately following GKS are described from two centres, which had prompted us to review the literature.

MR spectroscopy in sinus mucocele: N-acetyl mimics of brain N-acetylaspartate.

We describe MR spectroscopy in 2 patients with frontal sinus mucoceles that showed a dominant metabolite peak at 2.0-ppm chemical shift, simulating N-acetylaspartate (NAA) of normal neuronal tissue. In vitro analysis of postsurgical mucocele samples confirmed that the signal at 2.0 ppm was arising from the methyl moiety of an N-acetyl compound. This is probably caused by N-acetylgalactosamine or N-acetylglucosamine, which are glycoproteins found in normal respiratory mucus produced by the paranasal sinus epithelium.

The leukocyte common antigen-related protein tyrosine phosphatase receptor regulates regenerative neurite outgrowth in vivo.

Drosophila and leech models of nervous system development demonstrate that protein tyrosine phosphatase (PTP) receptors regulate developmental neurite outgrowth. Whether PTP receptors regulate neurite outgrowth in adult systems or in regenerative states remains unknown. The leukocyte common antigen-related (LAR) receptor is known to be present in rodent dorsal root ganglion (DRG) neurons; therefore, the well established model of postcrush sciatic nerve regeneration was used to test the hypothesis that LAR is required for neurite outgrowth in the adult mammalian nervous system. In uninjured sciatic nerves, no differences in nerve morphology and sensory function were detected between wild-type and LAR-deficient littermate transgenic mice. Sciatic nerve crush resulted in increased LAR protein expression in DRG neurons. In addition, nerve injury led to an increase in the proportion of LAR protein isoforms known to have increased binding affinity to neurite-promoting laminin-nidogen complexes. Two weeks after nerve crush, morphological analysis of distal nerve segments in LAR-deficient transgenic mice demonstrated significantly decreased densities of myelinated fibers, decreased axonal areas, and increased myelin/axon area ratios compared with littermate controls. Electron microscopy analysis revealed a significant twofold reduction in the density of regenerating unmyelinated fibers in LAR-/- nerves distal to the crush site. Sensory testing at the 2 week time point revealed a corresponding 3 mm lag in the proximal-to-distal progression of functioning sensory fibers along the distal nerve segment. These studies introduce PTP receptors as a major new gene family regulating regenerative neurite outgrowth in vivo in the adult mammalian system.

Cerebellar strokes: a clinical outcome review of 79 cases.

INTRODUCTION: Cerebellar infarcts and haemorrhages are relatively uncommon, accounting for less than 10% of all strokes. The objective of the present study was to quantify and compare the outcomes of patients with cerebellar infarct and those of patients with cerebellar haemorrhage, as well as to identify the risk factors that predict poor outcome in patients with cerebellar stroke. METHODS: We retrospectively reviewed the medical records of consecutive patients admitted to National University Hospital, Singapore, between 2004 and 2006, within one week of cerebellar stroke onset. Baseline data included demographics, concomitant comorbidities, and the presence or absence of brainstem compression and hydrocephalus (on computed tomography or magnetic resonance imaging). The Glasgow Outcome Scale and modified Rankin Score were used to assess outcome at discharge and at six months after discharge. RESULTS: A total of 79 patients with cerebellar stroke were admitted during the study period. Of these 79 patients, 17.7% died and 31.6% had poor outcomes at six months after discharge. Patients with cerebellar haemorrhage were found to be more likely to have poor outcomes as compared to patients with cerebellar infarct, both at discharge (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.3-14.1) and at six months after discharge (OR 5.2, 95% CI 1.6-17.2). When compared to small lesions (< 5 cm(3)), lesions > 20 cm(3) were significantly associated with poorer outcomes and the development of hydrocephalus and brainstem compression. CONCLUSION: Cerebellar strokes are a significant cause of morbidity and mortality. The outcomes of patients with cerebellar haemorrhage are more likely to be worse than those of patients with cerebellar infarct.

Gene expression along the cerebral-spinal axis after regional gene delivery.

We demonstrate here that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or cationic liposome: DNA complexes (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Gene expression was identified both within the spinal cord and the brain after intracerebroventricular or intrathecal injection of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathecal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene produced patchy, widely scattered areas of beta-Gal expression. The chloramphenicol acetyltransferase (CAT) reporter gene product reached peak levels between 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal injection. Intrathecal injection of the human granulocyte colony-stimulating factor (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine nerve growth factor (NGF) gene increased mNGF levels in the hippocampus, a target region for cholinergic neurons in the medial septum, and increased cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intracerebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes within the CNS. Efficient gene transfer into the CNS will facilitate the evaluation of gene function and regulation within the brain and spinal cord. We attempted to transfer and express genes within the brain and spinal cord by direct CNS injection of either DNA alone or CLDCs into the intraventricular and subarachnoid compartments. We show that intracerebroventricular or spinal cord (intrathecal) injection of either plasmid DNA alone or CLDCs produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the brain and the spinal cord. Intrathecal injection of the hG-CSF gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing the murine NGF gene increased mNGF levels in the hippocampus, and increased cholinergic neurotransmitter synthetic enzyme ChAT activity within the brain. Locoregional diffusion of gene products expressed by transfected meningeal lining cells into brain and spinal cord parenchyma could potentially target secreted proteins within brain and spinal cord regions relevant to neuropathological states while limiting peripheral side effects.

Second messenger regulation of mouse gonadotropin-releasing hormone gene expression in immortalized mouse hypothalamic GT1-3 cells.

Using a transgenic mouse derived GnRH expressing neuronal cell line, GT1-3, we studied the effects of activation of cAMP, Ca2+ and protein kinase C pathways by forskolin, ionomycin and the phorbol ester phorbol 12-myristate 13-acetate (PMA), respectively, upon gonadotropin-releasing hormone (GnRH) secretion, cellular peptide content, mRNA and RNA primary transcript levels. Forskolin, ionomycin and phorbol ester all caused an increase in GnRH secretion in GT1-3 cells in a time and dose-dependent manner during a short-term (1 h) static incubation. Prolonged treatment with forskolin (10 microM), ionomycin (1 microM) and PMA (10 nM) for 12 or 24 h resulted in significant decreases in GnRH mRNA levels. Time-course studies showed that the increases in GnRH secretion stimulated by forskolin, ionomycin and PMA were gradually attenuated over time in parallel with the decreases in mRNA expression. In contrast, there were only small and variable changes in the GnRH cellular content. Studies using a GnRH antagonist (100 microM) suggested that the released GnRH has a negative feedback effect on its own secretion. However, co-incubation with the GnRH antagonist did not alter the inhibitory effects on GnRH mRNA levels by the secretagogues. Further studies on the transcriptional effects of forskolin, ionomycin and PMA on GnRH gene expression in GT1-3 cells revealed that all three secretagogues suppressed GnRH RNA primary transcript levels, with forskolin having a slower time course of action. Thus, the inhibition of cytoplasmic GnRH mRNA, and presumably its synthesis, after 12-24 h of secretagogue treatment may be due at least in part to a suppression of GnRH gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of gonadotropin-releasing hormone gene transcripts in a mouse hypothalamic neuronal GT1 cell line.

We have characterized the nuclear and cytoplasmic RNA transcripts derived from the gonadotropin releasing hormone (GnRH) gene in a mouse hypothalamic neuronal GT1 cell line. Analyses of nuclear GnRH RNA precursors present in the GT1 cells by RNase protection assay show that there is no particular order of intron excision, suggesting the existence of multiple processing pathways. A similar pattern is observed in mouse preoptic area-anterior hypothalamus (POA-AH). In GT1 cells, approximately 5% of the total GnRH RNA transcripts are found in the nucleus. In contrast, in the POA-AH of mice, nuclear transcripts comprise 40% of the total GnRH transcripts. Thus the GT1 cells, while similar in overall GnRH RNA processing to mouse hypothalamic GnRH neurons, do not exhibit the high abundance of nuclear GnRH RNA transcripts seen in the rodent GnRH neuron in vivo. Quantitative analysis of the nuclear RNA species shows that the GnRH primary transcript comprises more than 90% of the total nuclear GnRH mRNA precursors in both GT1 cells and mouse POA-AH and thus GnRH processing intermediates account for fewer than 10% of these precursors. Using these probes, we have examined changes in GnRH primary transcript expression in GT1-7 cells. In the presence of RNA synthesis inhibitors, the half-life of the GnRH primary transcript was found to be quite short, approximately 18 min, suggesting that the level of primary transcript would reflect levels of GnRH gene transcription. When GT1-7 cells are treated with the phorbol ester PMA (phorbol, 12-myristate, 13-acetate) for 1 h, GnRH primary transcript levels decrease by approximately 70%. Supporting the hypothesis that GnRH primary transcript is a good indicator of GnRH gene transcription is the finding that 1 h of PMA treatment results in a similar (approximately 50%) decrease in GnRH gene transcription, as assayed by nuclear run-on assay. Our observation that GT1 cells resemble mouse hypothalamic GnRH neurons in their pattern of intron excision and in the ratio of primary transcript to other nuclear transcripts emphasizes the utility of these cells for studying the regulation of GnRH gene expression in this immortalized hypothalamic cell line.

Post-transcriptional regulation of the gonadotropin-releasing hormone gene in GT1-7 cells.

GT1-7 cells respond to treatment with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), with an inhibition of transcription of the proGnRH gene and decreases in GnRH mRNA levels. However, the timing of this decrease in GnRH mRNA levels suggests that a decrease in GnRH mRNA stability may be involved in addition to an inhibition of transcription of the proGnRH gene. To address this possibility, we treated GT1-7 cells with 100 nM PMA for 4 h and then monitored GnRH mRNA levels over time after blockade of GnRH gene transcription with DRB. PMA treatment caused GnRH mRNA half-life to decrease from 30 to 11 h. Then, to verify this observation, we examined changes in GnRH mRNA poly (A) tail length, which may be a reflection of mRNA turnover, following treatment of GT1-7 cells with PMA or vehicle for 0, 4, 8 or 24 h. The poly (A) tail was removed from half of the GT1 cytoplasmic RNA sample by digestion with RNase H and the difference in GnRH mRNA size with and without RNase H treatment was determined by Northern hybridization. PMA treatment (4 and 8 h) resulted in a significant decrease in the length of the GnRH mRNA poly (A) tail, consistent with a decrease in GnRH mRNA stability. This finding suggests that GnRH mRNA turnover is inducible by substances such as PMA. Our study indicates that a change in mRNA stability is one of a multiplicity of levels at which GnRH gene expression is regulated.

Protein synthesis-dependent and -independent mechanisms for the regulation of GnRH RNA transcript levels in GT1 cells.

The cellular mechanism for the suppression of GnRH gene expression by the phorbol ester PMA was investigated in GT1 cells. The protein synthesis inhibitor cycloheximide decreased GnRH primary transcript levels, indicating a protein synthesis requirement for basal GnRH transcription. PMA decreased GnRH primary transcript levels even in the presence of cycloheximide, indicating that the PMA suppression of GnRH gene transcription is protein synthesis-independent. In contrast, the PMA-inhibitory effect on GnRH cytoplasmic mRNA levels was significantly reduced or inhibited in the presence of cycloheximide or RNA synthesis inhibitors given within 4 h of PMA, suggesting a protein/RNA synthesis-dependent mechanism for the regulation of GnRH mRNA levels by PMA. Thus, the mechanism for the PMA inhibition of GnRH primary transcript is mediated through a protein and RNA synthesis-independent mechanism, while the decrease in GnRH mRNA levels occurs through a mechanism that involves the induction of new RNA and protein synthesis that happens within 4 h of PMA administration.

Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications.

OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of neuronal injury after brain ischemia, and decreased levels of NO have been implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH). In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in patients with SAH and correlated the levels with clinical grade and middle cerebral artery velocities measured with transcranial Doppler ultrasound. METHODS: All patients with spontaneous SAH documented on computed tomography and with an external ventricular drain inserted within 24 hours of hemorrhage were included in the study. A total of 16 patients were studied between August 1999 and August 2000. CSF was collected serially at the time of surgery and subsequently at daily intervals. It was collected during the time that the external ventricular drain remained patent and in situ. NO levels were measured by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical, Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96 to 168.16 micromol, with a median of 36.93 micromol. The levels were significantly elevated as compared with the control group (5.16 micromol, P < 0.05). The median NO level in patients with poor-grade SAH was 67.14 micromol as compared with 27.42 micromol in patients with good-grade hemorrhage (P < 0.05). No correlation was seen between CSF NO levels and middle cerebral artery velocities. The median NO level was 33.2 micromol in patients with a poor outcome as compared with 30.25 micromol in patients with a good outcome (P > 0.05). CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH, and the degree of elevation is higher in patients with poor-grade SAH.

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE: Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS: Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS: Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION: Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

Computer-aided stereotactic functional neurosurgery enhanced by the use of the multiple brain atlas database.

This paper introduces a computer-aided atlas-based functional neurosurgery methodology and describes NeuroPlanner, a software system which supports it. NeuroPlanner provides four groups of functions: 1) data-related for data reading, interpolation, reformatting, and image processing; 2) atlas-related for multiple atlases reading, atlas-to-data global and local registrations, two-way anatomical indexing, and multiple labeling in two and three dimensions; 3) atlas-data exploration-related for three-dimensional (3-D) display and real-time manipulation of cerebral structures, continuous navigation, two-dimensional (2-D), triplanar, 3-D presentations, and 2-D interaction in four views; and 4) neurosurgery-related for targeting, trajectory planning, mensuration, simulating the insertion of microelectrode, and simulating therapeutic lesioning. All operations, excluding atlas and data reading, are real time. The combined anatomical index of the multiple brain atlas database containing complementary 2-D and 3-D atlases has about 1000 structures per hemisphere, and over 400 sulcal patterns. Neurosurgical planning with mutually preregistered multiple brain atlases in all three orthogonal orientations is novel. The approach is validated with 24 intraoperative and postoperative datasets for thalamotomies, thalamic stimulations, pallidotomies, and pallidal stimulations. Its potential benefits include increased accuracy of target definition, reduced time of the surgical procedure by decreasing the number of tracts, facilitated planning of more sophisticated trajectories, lowered cost by reducing the number of microelectrodes used, reduced surgical complications, and the extra degree of confidence given to the neurosurgeon.

Tension pneumocephalus and pneumorachis secondary to subarachnoid pleural fistula.

A case of tension pneumocephalus and pneumorachis secondary to a subarachnoid pleural fistula after thoracic spinal surgery is described. This rare complication was diagnosed on CT. The imaging findings, significance and management of this unusual condition are discussed.

Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management.

BACKGROUND: The optimal treatment of hypertensive supratentorial intracerebral hemorrhage is still debated. Some studies have shown no improvement in survival or functional outcome after surgery when compared to conservative management while others have shown otherwise. METHODS: This study was a prospective trial, matching patients for hematoma volume and Glasgow Coma score on admission. RESULTS: There were a total of 34 patients. Seventeen were treated conservatively and 17 surgically. There was no significant difference between the two groups in terms of age, GCS, hematoma volume, or presence of intraventricular blood. At 3, 6, and 12-month follow-up, they were assessed using the Modified Barthel Index by a blinded observer. There was no difference between the two groups at 3, 6, or 12 months follow-up. The mortality rate was similar in the two groups. CONCLUSIONS: Based on this study and review of the literature, we cannot recommend routine evacuation of clots to treat these hemorrhages.

Functional neurosurgery aided by use of an electronic brain atlas.

The authors present their experience in the use of an atlas-based computer system for preoperative functional neurosurgery planning and postoperative analysis. It has also some potential for intraoperative support. The system is based on a deformable electronic version of "Atlas of Stereotaxy of the Human Brain" by Schaltenbrand and Wahren. This atlas is used for interactive segmentation and labelling of clinical data in two- and three dimensions, and for definition of stereotactic targets. The Schaltenbrand-Wahren atlas microseries are digitized, enhanced, segmented, labelled, aligned and organized into atlas volumes. They are mutually preregistered, and three-dimensional models of the structures are constructed. The atlas may be interactively registered with an actual patient's data. A computer system is developed which provides data interpolation, reformatting, registration, visualization, navigation, mensuration and path display and editing in two- and three dimensions. The system increases the accuracy of target definition, reduces the time of planning and the time of the procedure itself. It also constitutes a research platform for the construction of more advanced neurosurgery supporting tools and brain atlases.

Petrosal approach for a large right posterior cerebral artery (P2) aneurysm.

A seven year old girl presented with recurrent headaches Computed tomography (CT) magnetic resonance imaging (MRI) and angiography showed a 2 cm aneurysm at the P2 segment of the right posterior cerebral artery. The aneurysm was trapped successfully by a petrosal approach. The patient made an excellent recovery except for a transient fourth nerve palsy.

Non-traumatic spontaneous acute epidural haematoma -- report of two cases and review of the literature.

Epidural haematomas are usually associated with preceding head trauma. The entity of non-traumatic spontaneous acute epidural haematoma is rare and most commonly occurs in the presence of infectious disease. It can also occur in the presence of coagulopathy, vascular malformations of the dura mater and haemorrhagic tumours. Sickle cell disease, systemic lupus erythematosus, open heart surgery and haemodialysis have also been implicated as causative factors. The authors report two cases of spontaneous epidural haematomas (one of unknown aetiology and one from a coagulation disorder) and discuss the aetiological agents involved in this rarely described condition.

Tuberculoma of the brain--report of 2 cases and review of literature.

Tuberculomas of the brain are relatively uncommon in developed countries nowadays. We report the only two cases that were seen in our Department in the last five years. Both patients presented with seizures and were found to have space occupying lesions on cranial CT scanning. They had no past history of tuberculosis, no evidence of current extracranial tuberculosis and the diagnosis of tuberculoma was made at the time of surgical excision. Underdiagnosis of tuberculoma of the brain is likely to occur in industrialised countries where tuberculosis is rare. The radiological investigation of choice is CT scanning with contrast enhancement and the presence of a target lesion is considered to be pathognomonic of a tuberculoma. Most tuberculomas of the brain can be treated medically with antituberculous chemotherapy. We recommended obtaining a definitive histological diagnosis with CT-guided stereotactic techniques prior to commencing antituberculous therapy. Surgical excision is necessary in patients with raised intracranial pressure secondary to the lesion and not responding to medical therapy.

Traumatic posterior fossa extradural haematomas (PFEDH).

OBJECTIVES: While posterior fossa extradural haematomas (PFEDH) may lead to rapid neurological deterioration and death because of brainstem compression, prompt treatment often leads to a good outcome. The non-specific clinical signs and the rarity of this lesion in craniocerebral trauma adds to the difficulty in diagnosis. The aim of this study was to identify features which could lead to an early diagnosis. METHODS: Seventeen patients with posterior fossa extradural haematomas were operated on over 4 1/2 years, accounting for 7.5% of the 226 surgically operated extradural haematomas in the Department of Neurosurgery, Tan Tock Seng Hospital, Singapore. Four patients were excluded from this study due to non-availability of the case records. The remaining 13 patients formed the study group in this retrospective analysis. RESULTS: The majority of cases (77%) presented acutely within 24 hours. The mechanism of injury varied from a fall in 7 cases, a road traffic accident in 4 cases and assault in 2. Nine patients had evidence of external injury to the occiput, 8 patients had skull fractures, and diastasis of the lambdoid suture was seen in 2 cases. Presence of aerocele was noted in the CT scan of 4 cases. All 9 cases admitted with a high GCS score of more than 8 had a very good outcome. CONCLUSION: An early CT scan head is recommended if a combination of the following features is present: occipital soft tissue injury, drowsiness, occipital fracture or diastasis of the lambdoid suture.