Lymphatic outflow of cerebrospinal fluid is reduced in glioma.

Glioblastoma is a malignant brain tumor with mean overall survival of less than 15 months. Blood vessel leakage and peritumoral edema lead to increased intracranial pressure and augment neurological deficits which profoundly decrease the quality of life of glioblastoma patients. It is unknown how the dynamics of cerebrospinal fluid (CSF) turnover are affected during this process. By monitoring the transport of CSF tracers to the systemic blood circulation after infusion into the cisterna magna, we demonstrate that the outflow of CSF is dramatically reduced in glioma-bearing mice. Using a combination of magnetic resonance imaging (MRI) and near-infrared (NIR) imaging, we found that the circulation of CSF tracers was hindered after cisterna magna injection with reduced signals along the exiting cranial nerves and downstream lymph nodes, which represent the major CSF outflow route in mice. Due to blockage of the normal routes of CSF bulk flow within and from the cranial cavity, CSF tracers were redirected into the spinal space. In some mice, impaired CSF clearance from the cranium was compensated by a lymphatic outflow from the sacral spine.

Single amyloid-beta injection exacerbates 4-aminopyridine-induced seizures and changes synaptic coupling in the hippocampus.

Accumulation of amyloid-beta (Aß) in temporal lobe structures, including the hippocampus, is related to a variety of Alzheimer's disease symptoms and seems to be involved in the induction of neural network hyperexcitability and even seizures. Still, a direct evaluation of the pro-epileptogenic effects of Aß in vivo, and of the underlying mechanisms, is missing. Thus, we tested whether the intracisternal injection of Aß modulates 4-aminopyridine (4AP)-induced epileptiform activity, hippocampal network function, and its synaptic coupling. When tested 3 weeks after its administration, Aß (but not its vehicle) reduces the latency for 4AP-induced seizures, increases the number of generalized seizures, exacerbates the time to fully recover from seizures, and favors seizure-induced death. These pro-epileptogenic effects of Aß correlate with a reduction in the power of the spontaneous hippocampal network activity, involving all frequency bands in vivo and only the theta band (4-10 Hz) in vitro. The pro-epileptogenic effects of Aß also correlate with a reduction of the Schaffer-collateral CA1 synaptic coupling in vitro, which is exacerbated by the sequential bath application of 4-AP and Aß. In summary, Aß produces long-lasting pro-epileptic effects that can be due to alterations in the hippocampal circuit, impacting its coordinated network activity and its synaptic efficiency. It is likely that normalizing synaptic coupling and/or coordinated neural network activity (i.e., theta activity) may contribute not only to improve cognitive function in Alzheimer's disease but also to avoid hyperexcitation in conditions of amyloidosis.

Differential Diagnoses and Their Implications of Dandy-Walker Malformation or Isolated Cisterna Magna, a Case Study: Baby V.

We explore the outcome of a fetus with a posterior fossa abnormality thought to be a Dandy-Walker malformation based on prenatal ultrasound imaging. The infant was later diagnosed by magnetic resonance imaging (MRI) as having an isolated cisterna magna. When assessing brain abnormalities, there is increased accuracy of prenatal MRI versus prenatal ultrasound. Accurate diagnosis of an infant is paramount so that an inheritance pattern, risk of recurrence, involvement of other systems, and a prognosis can be determined. Communicating with the family and supporting them with the correct information is then enhanced. It should be standard protocol to obtain a fetal MRI if an abnormal prenatal ultrasound of the brain is detected. Further research is needed to assess the accuracy of using MRI versus ultrasonography prenatally to diagnose posterior brain abnormalities.

Quadrigeminal cisterna lipoma: report of two cases and literature review / Lipoma da cisterna quadrigeminal: relato de dois casos e revisão da literatura

Intracranial lipomas are congenital, benign and slow-growing tumors. The incidence were 0.1 to 0.5 percent of all primary brain tumors and are often diagnosed in incidental findings of neuroradiological investigation. Lipoma in quadrigeminal region occurs in 25 percent of intracranial lipomas and has been reported as lipomas in quadrigeminal cistern (perimesencephalic cistern), quadrigeminal plate, ambiens cistern or superior medullary velum. MRI is the most major exam. The treatment is conservative in most cases, surgical removal is hampered by their deep location and contiguous with adjacent neurovascular structures. The authors report two cases of lipoma in the quadrigeminal region, incidental findings and discuss the clinical findings, neuroimaging and treatment.

Lipomas intracranianos são tumores congênito, benigno e de crescimento lento. Sua incidência é de 0.1 a 0.5 por cento de todos os tumores cerebrais primários e são frequentemente diagnosticados em achados incidental de investigação neuroradiológica. Lipoma na região quadrigeminal ocorre em 25 por cento dos lipomas intracranianos e tem sido relatados como lipomas na cisterna quadrigeminal (cisterna perimesencefálica), placa quadrigeminal, cisterna ambiens ou véu medular superior. O exame de eleição é ressonância magnética. O tratamento é conservador na maioria dos casos, a remoção cirúrgica é dificultada pela sua localização profunda e da contiguidade com estruturas neurovasculares adjacentes. Os autores relatam dois casos de lipoma na região quadrigeminal achados incidentalmente e discutem os achados clínicos, imagem e tratamento.

Developmental outcome of children with enlargement of the cisterna magna identified in utero.

An enlarged cisterna magna can be identified during routine ultrasound screening in the second half of pregnancy. It is important to be able to give an accurate prognosis. We evaluated the developmental outcome of these children. A total of 29 fetuses with a large cisterna magna identified in utero were compared to 35 children with a normal fetal ultrasound. The children were evaluated by the Gesell Developmental Schedules and the Peabody Developmental Motor Scale. The study group showed a significantly worse performance in the Gesell test. However, the overall performance for both groups was within normal limits. Four children in the study group had a borderline developmental quotient. Both groups performed similarly in the Peabody test. Walking age was significantly delayed in the study group. Children with an enlarged cisterna magna may be at risk for mild developmental delay. In cases of nonisolated enlargement of the cisterna magna, the outcome may be guarded.

Severe intracranial hypertension in slit ventricle syndrome managed using a cisterna magna-ventricle-peritoneum shunt.

OBJECT: Severely increased intracranial pressure (ICP) can be life threatening in patients who had previously undergone shunt treatment but who do not experience ventricular enlargement. The authors analyzed the utility of placing shunts into the cisterna magna concurrently with ventricular shunts in patients who were not candidates for lumboperitoneal (LP) shunt placement. METHODS: Ten patients treated with cisterna magna-ventricle-peritoneum (CMVP) shunts for complex problems of shunt function were reviewed retrospectively. All patients had documented increases in ICP and ventricles that did not expand despite life-threatening increases (> 80 mm Hg in one case) in ICP. Between 1995 and 2003, 10 patients (four males and six females, age range 4-32 years) were identified as having life-threatening increases in ICP despite small or slit-like ventricles on imaging studies. Each episode was documented with intraparenchymal pressure monitoring. All patients had documented ventricular catheter failures at the time of the intervention, and all had undergone at least one previous attempt to treat the condition with a valve upgrade and replacement of the ventricular catheter. Three patients had achondroplasia, four had spina bifida, and three had a preexisting Chiari malformation Type I. All patients improved after the procedure, and none suffered permanent complications. For at least 48 hours after surgery, all patients underwent intraparenchymal monitoring of ICP (an intraparenchymal monitor was used that documented normal ICP). CONCLUSIONS: The CMVP shunts are an excellent option for patients who are not candidates for LP shunts but who have high ICP and ventricles that do not enlarge at shunt failure. The ability to access the spinal fluid in the cortical subarachnoid space presumably accounts for this success.

Nitric oxide metabolites in cisternal CSF correlate with cerebral vasospasm in patients with a subarachnoid haemorrhage.

BACKGROUND: The pathogenesis of cerebral vasospasm is likely to be multifactorial. Exposure of the adventitia of large cerebral arteries to blood breakdown products initiates a cascade of changes in both morphology and vasomotor regulation of the exposed vessels. The role of nitric oxide (NO) in development of cerebral vasospasm process is controversial. Basal cerebral vascular tone requires the continuous release of NO, nevertheless NO is involved in free radical mediated injury of endothelial cell membrane. Concentrations of nitrate/nitrite (stabile endproducts of NO metabolism) were studied in cisternal cerebrospinal fluid (cCSF) in patients suffering from aneurysmal subarachnoid haemorrhage (SAH). METHOD: 21 patients suffering from aneurysmal SAH were investigated. Treatment included aneurysm clipping, cisternal drainage of CSF and intravenous nimodipine in all patients as well as tripple H therapy when indicated. TCDS was performed on a daily basis. A mean flow velocity of more than 150 cm/sec and the development a delayed neurological deficit was defined as vasospasm. CSF samples were collected on the day of surgery and for the 7 days following. NO-M (nitrite and nitrate) were measured using a commercially available test kit. FINDINGS: 5 of 21 patients developed clinically symptomatic vasospasm. There was a significant difference in NO levels between the groups. Patients with cerebral vasospasm showed significantly higher levels of NO-M in CSF than patients with a uncomplicated follow-up between day 2 and 8. INTERPRETATION: Our preliminary results indicate that SAH leads to an increase in NO-M in CSF. This increase of NO-M significantly correlates with the flow velocities in TCDS measurement suggesting that NO plays an important role in the pathogenesis of cerebral vasospasm.

Intracisternal PYY inhibits gastric lesions induced by ethanol in rats: role of PYY-preferring receptors?

We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23+/-2% of the gastric corpus in 1 h. PYY (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro34]PYY (PYY-preferring/Y1/Y5/Y4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4+/-2.2%, 11.4+/-3.1%, 8.6+/-2.9% and 5.4+/-2.2%, respectively. PYY3-36, (Y2/Y4 subtypes), [Leu31, Pro34]NPY (Y1/Y5), NPY (Y3/Y1/Y5/Y2) and pancreatic polypeptide (PP, Y4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro34PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9+/-2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu31, Pro34]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y1/Y5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol.

Combined cisternal drainage and intrathecal urokinase injection therapy for prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage.

The effect of cisternal drainage and intrathecal urokinase injection in preventing symptomatic vasospasm (SVS) after aneurysmal subarachnoid hemorrhage was studied in 60 patients with uniform background (Hunt & Kosnik grade III, younger than 70 yrs, undergoing surgery within 72 hrs after hemorrhage). The incidence of permanent neurological deficits caused by vasospasm was 5/16 without cisternal drainage, 5/34 with drainage alone, and 1/10 with drainage and urokinase injection. Analysis of patients without postoperative cisternal drainage showed the amount of subarachnoid clot on the initial computed tomographic scan was closely related to the occurrence of SVS (p < 0.05, unpaired t test). Analysis of patients with cisternal drainage showed the amount of bloody cerebrospinal fluid (CSF) drained during the 10 days after surgery and the duration of drainage placement were critical in preventing vasospasm (p < 0.05, unpaired t test). Greater CSF drainage significantly reduced the incidence of permanent neurological deficits caused by vasospasm (p < 0.01, chi 2), but significantly increased the incidence of hydrocephalus requiring shunt procedures (p < 0.01, chi 2). Urokinase injection via cisternal drainage achieved a further reduction in the occurrence of SVS. Intrathecal thrombolytic therapy after aneurysmal surgery is an effective method for SVS prophylaxis, and CSF drainage (> 1500 ml for 10 days) enhances the effect.

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.

[Cerebrospinal fluid dynamics in experimental subarachnoid hemorrhage]. / Zur Liquordynamik während experimenteller Subarachnoidalblutung.

To investigate the acute effects on intracerebral pressure, intracranial reserve capacity and CSF absorption resistance, a subarachnoidal haemorrhage was induced experimentally in a cat by bolus injection or continuous infusion of autologous blood into the cisterna magna. Intracisternal bolus injection resulted in a brief steep increase in intracranial pressure. 30 or 60 minutes after the haemorrhage the median intracranial pressure is slightly increased, the reserve capacity markedly reduced and the CSF absorption resistance considerably enhanced. During intracisternal blood infusion there is a continuous intracerebral pressure rise that persists to the end of the infusion and decrease again within a short time. This intracranial pressure behaviour is due to the simultaneous reduction of intracranial reserve capacity and the increase in CSF absorption resistance during the blood infusion.