Gravitational valves in supine patients with ventriculo-peritoneal shunts.

BACKGROUND: In the subgroup of bedridden hydrocephalic patients with ventriculo-peritoneal shunts and gravitational valves, we occasionally observed persisting hydrocephalic complaints even when mechanical or infection-related obstruction was excluded. METHODS: To investigate the cause of these hydrocephalic symptoms, in vitro and in vivo analyses were used to determine valve opening, intra-abdominal and hydrostatic pressure of an Aesculap-Miethke 10/40 cm H2O gravitational valve at different angles of upper body and head inclination. FINDINGS: Since hydrostatic pressure is lacking, the resulting intra-ventricular pressures are shown to peak up to 27 cm H2O in supine patients with head, but not upper body inclined. CONCLUSIONS: We conclude that in the subgroup of bedridden patients with ventriculo-peritoneal shunts and gravitational valves, upright posture is a prerequisite for proper cerebrospinal fluid drainage.

Minimally invasive dorsal percutaneous spondylodesis for the treatment of adult pyogenic spondylodiscitis.

BACKGROUND: Most adult patients with pyogenic lumbar or thoracic spondylodiscitis are treated with an external orthosis and antimicrobial therapy for several weeks to months. If surgical intervention is required, a combined anterior and posterior approach for debridement and fusion with autologous bone graft or titanium mesh cage is usually performed. METHOD: We here report on our experience with the use of a minimally invasive percutaneous dorsal pedicle screw-rod spondylodesis in adult patients with pyogenic lumbar or thoracic spondylodiscitis. FINDINGS: Eight patients with lumbar, one with thoracolumbar and three with thoracic pyogenic spondylodiscitis with a mean back pain of 9/10 on the visual analog scale (VAS) and without corresponding neurological deficits were treated. Immediately after the operation, we calculated a significant reduction of the back pain on the VAS to 1.7, of leukocyte counts and C-reactive protein levels. After a mean of 61 days of continuous antimicrobial therapy during full mobilization, all patients were pain free, and leukocyte counts as well as C-reactive protein levels were normalized. CONCLUSIONS: We conclude that minimally invasive percutaneous fixation is a feasible and effective technique to achieve immediate pain release, avoid long-term immobilization and overcome the disadvantages of a dorsoventral procedure. However, surgical complications and possible follow-up procedures supplement the patients' risks of adverse reactions of the disease.

Bedside catheter evacuation of predominantly isolated traumatic supratentorial hemorrhage.

BACKGROUND: Predominantly isolated intracerebral hemorrhage (ICH) is a rare complication after traumatic brain injury that tends to occur in patients with coagulation disorders. METHODS: We developed a minimally-invasive free-hand bedside catheter evacuation procedure using 3D-computerized tomography reconstruction imaging. Twelve patients were retrospectively analyzed. RESULTS: Average duration of the procedure was approximately 15 minutes. After catheter placement, urokinase-lysis ensured successful hemorrhage evacuation. Mean Glasgow coma scale at admission was 10 and mean hemorrhage diameter was 6.3 x 3.9 x 4.2 cm, or 55 mL. Mean hemorrhage reduction was 37 mL or 66% in a mean of 4 days. No catheter-related complications were observed. The 30-day and 6-month mortality rates were 16%. Mean extended Glasgow outcome scale at discharge was 4. After a mean of approximately 19 months, nine patients had a favorable, two an unfavorable outcome. One was lost to follow-up. CONCLUSIONS: In comparison with previously published results, free-hand bedside catheter evacuation is a quick and easy-to-apply technique to evacuate predominantly isolated traumatic supratentorial hemorrhage that can be performed in any intensive care unit.

Transient intradural catheter lysis in a patient with a diffuse and elongated subdural hematoma of the spine due to trauma. Case report.

The often extended and elongated configuration of a diffuse subdural hematoma of the spine makes it impossible to completely evacuate with common neurosurgical approaches. The authors describe the complete evacuation of a diffuse subdural hematoma of the entire spine due to trauma in a patient who suffered myelopathy and paraplegia in succession, by using transient subdural catheter lysis. After the patient underwent a partial hemilaminectomy at T7-8 and L2-3 using a lateral transmuscular approach, a 15 cm-long intraventricular catheter was inserted at each hemilaminectomy site and connected to an external ventricular drainage system in a procedure lasting 1 hour. Subsequently, 5000 IU of urokinase was applied four times daily for 30 minutes each time over the next 5 days. Two months later, the patient presented with spastic paraparesis Manual Muscle Test Grade 4/5. Magnetic resonance (MR) imaging revealed no catheter-related complications. The authors conclude from this case that transient catheter lysis may be an effective and gentle method to treat diffuse and elongated subdural hematomas of the spine due to trauma. A larger series needs to be analyzed, however, to address the indications and limitations of the technique compared with conventional open surgery. Such evaluation should include serial MR imaging and electrophysiological examination.

Endostatin/collagen XVIII accumulates in patients with traumatic brain injury.

In patients with traumatic brain injury (TBI), hypoperfusion contributes to ongoing and expanding areas of neuronal damage long after the initial trauma has ceased. In order to evaluate whether the antiangiogenic protein endostatin may play a role in this process, we analyzed its spatial distribution in brains of 18 patients with TBI. We observed an increase of endostatin/collagen XVIII(+) macrophages/microglial cells but not astrocytes up to day 14 and a consequent decrease to day 16 post-TBI. In addition, paracellular endostatin/collagen XVIII deposits were detected. In vitro experiments revealed that microglial endostatin release is induced predominantly by hypoxia and, to a lesser extent, by reactive oxygen intermediates. Common NO synthase inhibitor pharmacotherapy with aminoguanidine and L-NAME completely abolished endostatin release from microglial cells, raising hopes of altering endostatin release in vivo.

Tako-tsubo cardiomyopathy: reversible heart failure with favorable outcome in patients with intracerebral hemorrhage. Case report.

In patients with intracerebal hemorrhage, cardiac dysfunction is a common phenomenon. Tako-tsubo cardiomyopathy is characterized by complete reversibility and therefore may constitute an entity with a favorable outcome. In this case report the authors describe a previously healthy 23-year-old man with no history of cardiac disease who suffered a severe fourth ventricular hemorrhage due to an angioma of the vermis cerebelli. After emergency surgery, progressive tachycardia, fibrillation, and electromechanical decoupling developed in the patient. An echocardiogram revealed left ventricular apical akinesia and basal hyperkinesis characteristic of tako-tsubo cardiomyopathy. One week after admission, cardiac function was normal. Tako-tsubo cardiomyopathy differs from common cardiac dysfunction in its reversible nature. This characteristic must be taken into consideration when treating patients with intracerebral hemorrhage to avoid misclassification of the disease.

Aberrant neuronal and paracellular deposition of endostatin in brains of patients with Alzheimer's disease.

Cerebrovascular pathology is common in Alzheimer's disease (AD) and is considered to contribute to cerebral malfunction. However, distinct antiangiogenic proteins that accumulate in AD brains have not yet been identified. Endostatin is a 20 kDa C-terminal fragment of collagen XVIII that, when added exogenously, inhibits endothelial proliferation and migration in vitro and angiogenesis and tumor growth in vivo by inducing apoptosis in endothelial cells. We produced a monoclonal antibody directed against endostatin and observed significantly more (p < 0.0001) immunoreactive cortical neurons in AD brains compared with age-matched neuropathologically unaltered controls. High numbers of extracellular and frequently perivascular endostatin deposits were detected in the cerebral hemispheres. Double-labeling experiments revealed colocalization of endostatin in amyloid-beta(1-40) (Abeta(1-40)), tau protein, and periodic acid-Schiff stain-positive plaques that were surrounded by focal gliosis. Western blotting revealed more 20 kDa endostatin in an AD patient compared with a control. In unstimulated SKNSH supernatants, endostatin was detected that increased predominantly after hypoxia in supernatants and cellular lysates. Abeta(1-40) (80 microg/ml) supplementation to SKNSH neurons for 24 hr completely abolished the release of endostatin. These data show that endostatin is released by neurons to accumulate in amyloid plaques in Alzheimer's disease. Induction by hypoxia and complete abrogation of endostatin release after Abeta(1-40) challenge reveals intricate interactions between the two proteins and opens new avenues for the development of novel treatment strategies of AD patients.

Endothelial endostatin release is induced by general cell stress and modulated by the nitric oxide/cGMP pathway.

Endostatin is a 20 kDa carboxyl-terminal fragment of collagen XVIII that, when added exogenously, inhibits endothelial proliferation and migration in vitro and angiogenesis and tumor growth in vivo. Previous results showed endostatin/collagen XVIII labeling in few endothelial cells in human glioblastoma multiforme. We have now observed constitutive release of endostatin from one of four endothelial cell lines. Induction of endostatin release was observed after H2O2, an in vitro model of cell stress, CoCl2, a model of hypoxia, and by IFN-gamma challenge. Endostatin expression and release was reduced by the nitric oxide synthase inhibitors aminoguanidine and L-NAME and induced by the NO synthase-independent NO donors sodium nitroprusside (SNP) and spermine-NONO-ate. SNP-mediated endostatin induction was abrogated by the soluble guanylate cyclase inhibitor 1H-(1.2.4) oxadiazolo (4,3-A) quinoxalin-1-one. Adenoviral endostatin transduction resulted in the release of endostatin from endothelial cells and in down-regulation of iNOS (NOS2) and eNOS (NOS3), and surprisingly in a 10% induction of PCNA. These results describe the modulation of endostatin release by the NO signaling cascade and provide important new pharmacological information for the systemic induction of endogenous endostatin release by common NO donor pharmacotherapy.

The allograft inflammatory factor-1 family of proteins.

The allograft inflammatory factor-1 (AIF-1) is a 17 kDa interferon-gamma-inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA class III genomic region. Three proteins are probably identical with AIF-1 termed Iba1 (ionized Ca(2+)-binding adapter), MRF-1 (microglia response factor) and daintain. Considerable but not complete sequence identity with AIF-1 has been described for IRT-1 (interferon-responsive transcript), BART-1 (balloon angioplasty-responsive transcript), and other, yet unassigned alternatively spliced variants. In this review, genomic and functional characteristics of AIF-1-related proteins are summarized and a common nomenclature is proposed.

Angiogenic proteins in brains of patients who died with cerebral malaria.

In cerebral malaria (CM), microvascular activation accompanies blood-brain barrier dysfunction which in turn represents the pathophysiological basis of neurological impairments in affected patients. To dissect the molecular basis of this process, we analyzed localization of proangiogenic vascular endothelial growth factor (VEGF), its receptor vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1), of downstream VEGF effectors matrix-metalloproteinase-1 (MMP-1) and connective tissue growth factor (CTGF), and of VEGF-interacting antiangiogenic thrombospondin-1 and -independent angiostatin in brains of patients who died with CM and controls by immunohistochemistry and Western blotting experiments. Most prominently, we detected more VEGF(+) astrocytes in CM patients and deposition of Flt-1 in Dürck's granulomas. MMP-1 and thrombospondin-1 accumulated in macrophages/microglial cells in Dürck's granulomas. In one CM patient, massive amounts of CTGF were detected as perivascular paracellular deposits. Angiostatin was observed in the serum of 2/7 control but in no CM patients. These data demonstrate the activation of the proangiogenic VEGF signaling cascade in patients with CM, probably reflecting compensatory mechanisms of general and focal brain hypoxia observed in these patients.

Accumulation of endostatin/collagenXVIII in brains of patients who died with cerebral malaria.

Endostatin is a 20 kDa C-terminal fragment of collagenXVIII that, when added exogenously, inhibits angiogenesis by inducing apoptosis of endothelial cells. In cerebral malaria (CM), blood-brain barrier dysfunction is a hallmark alteration in the formation of edema, inflammation, hemorrhage and Dürck's granulomas that are thought to represent the histopathological basis of neurological impairments observed in CM patients. We now analyzed endostatin/collagenXVIII expression in brains of seven patients who died with CM and in seven control patients by immunohistochemistry double-labeling experiments. Endostatin/collagenXVIII immunoreactive macrophages/microglial cells accumulated predominantly in Dürck's granulomas. Some immunoreactivity was observed in macrophages located in cerebral capillaries with deposition of malarial pigment and sequestration, but almost no immunoreactivity was detected in ring hemorrhages. Focal accumulation of endostatin/collagenXVIII in granulomas but not in ring hemorrhages of CM brains suggests a novel process that is involved in the destruction of endothelial cells at the time of Dürck's granuloma formation.

Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease.

Cyclooxygenases (COXs) mediate inflammation, immunomodulation, blood flow, apoptosis, and fever in various diseases of the brain. Whereas COX-2 is cytokine inducible, COX-1 is expressed by macrophages/microglial cells that accumulate in pathological foci. We analyzed the localization of COX-1 and COX-2 in postmortem cortex slices of eight patients who died with sporadic Creutzfeldt-Jakob disease (CJD) and four neuropathologically unaltered controls by immunohistochemical double-labeling, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blotting experiments. In healthy brains, COX-1 was expressed by single macrophages/microglial cells and COX-2 by disseminated neurons. In patients with CJD, significantly (p = 0.0195) more COX-1-expressing macrophages/microglial cells were detected adjacent to neurons. COX-2 expression was predominantly observed in neurons, and their number was significantly higher (p < 0.0001) compared to controls. RT-PCR and Western blotting revealed more COX-1 and COX-2 mRNA and protein in one CJD patient than in one control patient. These data show that accumulation of COX-1-expressing macrophages/microglial cells and COX-2-expressing neurons might represent important regulatory mechanisms in the complex process of neuronal degeneration in CJD patients.

Accumulation of the proinflammatory cytokine endothelial-monocyte-activating polypeptide II in ramified microglial cells in brains of Borna virus infected Lewis rats.

Borna disease virus (BDV) infection of adult Lewis rats induces a severe and often fatal neurologic disease characterized by a massive mononuclear meningo-encephalitis, and activation of microglial cells. Therefore, we analyzed expression of endothelial monocyte activating polypeptide II (EMAP II) by immunohistology as a marker for activation of microglial cells in BDV infected rat brains. EMAP II is a chemotactic peptide, inducing activation of macrophages and endothelial cells, and is considered a proinflammatory mediator of the innate immune system. An up to 30-fold increase in numbers of EMAP II+ microglial cells and a massive expression by infiltrating macrophages at perivascular inflammatory foci was observed in infected brains, with a maximum on day 25 after infection. These results provide evidence that EMAP II contributes to immune responses in inflammatory processes caused by viral infections.

Macrophages/microglial cells in patients with cerebral malaria.

Cerebral malaria is a life threatening sequel of Plasmodium falciparum infection and contributes significantly to malaria mortality, especially among children. Accumulation of macrophages and proliferation of microglial cells play key roles in cerebral malaria and are thought to contribute to the pathophysiological alterations observed in these patients, which include enhanced adherence of infected erythrocytes to the cerebral vasculature by expression and secretion of proinflammatory molecules, disruption of the blood-brain barrier, recruitment of other inflammatory cells to the lesion site. In this review, recent advances in the understanding of the involvement of macrophages/microglial cells in the development of cerebral malaria are summarized.

Galectin-3 labeling correlates positively in tumor cells and negatively in endothelial cells with malignancy and poor prognosis in oligodendroglioma patients.

BACKGROUND: Galectin-3 modulates cell growth, transformation and metastasis in a wide range of neoplasms. PATIENTS AND METHODS: We analyzed galectin-3 expression in a total of 69 oligodendroglioma tissue samples by immunocytochemistry double labeling and RT-PCR experiments. RESULTS: Galectin-3 expression was observed in oligodendrocytes, endothelial cells and macrophages/microglial cells in areas of solid tumor growth. Significantly fewer galectin-3+ oligodendroglioma cells and macrophages/microglial cells were detected in WHO grade II oligodendrogliomas than in their matched relapses and in WHO grade III anaplastic oligodendrogliomas. Inversely, significantly more galectin-3+ endothelial cells were detected in WHO grade II oligodendrogliomas than in their matched relapses and in WHO grade III anaplastic oligodendrogliomas. Patients with low endothelial galectin-3 labeling scores in primary oligodendrogliomas and anaplastic oligodendrogliomas had significantly shorter time to progression and overall survival than patients with high endothelial galectin-3 labeling scores. CONCLUSION: We conclude from these data that the cell-type specific expression of galectin-3 is differentially involved in oligodendroglioma pathology.

Recurrent spinal fistula as result of a rare combination of a perimedullary and peridural spinal fistula: case report.

OBJECTIVES: We report on a patient with the combination of a peridural and a perimedullary spinal fistula, which manifested consecutively. The clinical course and diagnostic steps reveal important observations helpful in the management of this pathology. CASE PRESENTATION: A 61-year-old male patient presented with a six-month history of progressive weakness of the lower limbs. Magnetic resonance imaging revealed edema and dilated spinal veins of the lower thoracic spinal cord. Spinal angiography confirmed the diagnosis of spinal dural fistula at level T9 on the left. The patient underwent surgery and the fistula was surgically excised. Two months after initial improvement, the clinical symptoms of lower limb weakness recurred. On re-angiography a spinal perimedullary fistula was found at level T7 that was not apparent on the previous angiogram and on the postoperative control angiogram. The patient underwent surgery again, and the second fistula was also excised. The clinical symptoms subsequently improved. CONCLUSION: The interesting point in this case was the rare combination of a peridural and a perimedullary spinal fistula. They presented consecutively and could not be identified simultaneously on the first angiogram. Only after closure of the first fistula did the second become apparent. We believe that this may be a result of a postoperative pressure change in the venous system of the cord. After closure of the first fistula, the arterio-venous (AV) shunt of the second fistula developed gradually. The possibility of a second fistula should be considered in the presence of persistent edema of the cord on magnetic resonance imaging (MRI) and subsequent clinical deterioration.

Hemorrhage rates of external ventricular drain (EVD), intracranial pressure gauge (ICP) or combined EVD and ICP gauge placement within 48 h of endovascular coil embolization of cerebral aneurysms.

OBJECT: In single patients with a cerebral aneurysm an external ventricular drain (EVD), an intracranial pressure (ICP) gauge or a combined EVD and ICP gauge placement is necessary after coil embolization and initiation of postprocedural anticoagulation. The aim of this study was to examine the hemorrhage rates of drain placement within 48 h after aneurysm coiling and under anticoagulation or antiplatelet therapy. METHODS: We retrospectively analyzed hemorrhage rates of EVD, ICP gauge or combined EVD and ICP gauge placement in 27 patients within 48 h after coil embolization under different anticoagulation or antiplatelet schemes (heparin, acetylsalicylic acid, clopidogrel). In patients with continuous heparin via perfusor the application was stopped periprocedurally. The results were compared to literature. RESULTS: Four hemorrhages (14.8%) were observed. Three hemorrhages were petechial and one was by definition a larger hemorrhage with 8 mm×10 mm in diameter. CONCLUSIONS: EVD, ICP gauge or combined EVD and ICP gauge placements within 48 h after cerebral aneurysm coiling and under different anticoagulation or antiplatelet regimens seem to have no increased risk of hemorrhages compared to literature.

Minimally invasive revision of a C2 isthmus screw.

OBJECTIVE: We present a novel technique for minimally invasive revision of a cervical isthmic screw via two 18-mm transmuscular tubular accesses. METHODS: A 55 year old male with combined anterior and posterior instrumentation after corpectomy of C3 to C4 complained of persistent neck pain and reduced head mobility in the follow-up examination. Isthmic screws had been placed in C2 and pedicle screws in C5. The system used is a versatile modular screw-rod system for the fixation of the occipito-cervico-thoracic spine. The patient's complaints were attributed to an inappropriately placed C2 isthmus screw. The screw was approximately 3 mm too long and perforated the C1-C2 facet joint on the left side. We replaced the screw by a shorter one through a minimally invasive transmuscular tubular approach. RESULTS: The transmuscular tubular access offered an adequate exposure of the screw head. The special features of the versatile modular fixation device allowed for screw easing, removal, replacement, and tightening through the tube. The symptoms of the patient resolved completely. Intraoperative blood loss and postoperative approach-associated pain were negligible. CONCLUSION: We conclude that in case of dorsal cervical fixation with a versatile modular screw-rod system, a minimally invasive transmuscular approach for revision of an isthmic screw may be a good alternative to open surgery.

A very rare cause of low-back pain and sciatica: deep vein thrombosis due to absence of the inferior vena cava mimicking the clinical and radiological signs of lumbar disc herniation.

The authors report a very rare cause of low-back pain and sciatica in a patient with iliac vein thrombosis attributed to absence of the infrarenal segment of the inferior vena cava (IVC) with massively dilated venous collaterals draining via a paraspinal plexus into the azygous system. This 21-year-old man presented with acute low-back pain radiating to the left ventral thigh. The initial CT scan revealed an intraspinal lesion that mimicked lumbar disc herniation. Further clarification revealed an iliac vein thrombosis, which was triggered by the absence of the infrarenal segment of the IVC, a very rare vascular anomaly. Collateral venous return was developed and led to lumbar varicosities and epidural vein engorgements. Laboratory examinations revealed factor V mutation as a predisposing factor for thrombosis. The patient's symptoms were relieved with anticoagulation and antiinflammatory therapy. Absence of the infrarenal IVC associated with iliac vein thrombosis should be regarded as a very rare cause of radicular and low-back pain, and this condition can mimic the clinical and radiological signs of lumbar disc herniation. Sciatica might be the first clinical manifestation of this rare venous anomaly.

Cerebral vasospasm in shunt infection.

OBJECTIVE: In bacterial shunt infection, CNS inflammation is a frequently observed complication that may cause vascular complications including vasospasms. Here, we describe the first patient with shunt infection-induced cerebral vasospasms. METHODS: A 35 year old woman with a ventriculoperitoneal shunt that was implanted years before developed facial nerve palsy and somnolence one week before admission to the hospital. RESULTS: After admission, the shunt was removed, and an external ventricular drainage was inserted. Microbiological analyses revealed coagulase-negative Staphylococcus on abdominal and cranial catheters. Follow-up NMR showed infarctions. Transcranial doppler sonography and cerebral arteriography revealed severe generalized cerebral vasospasms. Inspite of triple-H therapy and intraarterial spasmolysis, bilateral anterior and media artery infarction evolved. The patient was dismissed in a vegetative state. CONCLUSIONS: This case shows that severe cerebral vasospasms are a serious complication in patients with bacterial shunt infection that should be considered in patients, that don't improve following adequate antibiotic treatment.