Intraoperative 3D fluoroscopy in stereotactic surgery.

BACKGROUND: Intraoperative localisation of a stereotactic probe remains challenging. Stereotactic X-ray, the "gold standard", as well as intraoperative magnetic resonance (MRI) and computed tomography (CT), require a dedicated operating room (OR). Fluoroscopy with crosshairs confirms only grossly the target position. An alternative would be a mobile three-dimensional (3D) fluoroscopy C-arm. To our knowledge, this is the first report on 3D C-arm fluoroscopy to verify stereotactical trajectories. The objective was to assess the feasibility of using a 3D C-arm to verify the intraoperative trajectory and target. METHODS: A total of 12 stereotactic trajectories in 10 patients were analysed, comprising 8 biopsies and 4 electrode trajectories. The fluoroscopic scan was performed after implantation of the deep brain stimulation electrode or after advancing the biopsy needle to the tumour. An image set is acquired during a rotation of the 3D C-arm. The image set is reconstructed and merged to the preoperative CT scan. Calculating the vector error and the deviation assesses target and trajectory accuracy. RESULTS: The mean trajectory deviation was 0.6 mm (±0.54 mm) and the mean vector error was 1.44 mm (±1.43 mm). There was no influence on the surgical time and the mean irradiation dosage was 401.9 cGycm(2). CONCLUSIONS: This target and trajectory verification is feasible. Its accuracy seems comparable with MRI and CT. There is no additional time consumption. Irradiation is comparable with stereotactic X-ray.

Decompressive hemicraniectomy in subarachnoid haemorrhage: the influence of infarction, haemorrhage and brain swelling.

OBJECTIVE: To analyse decompressive hemicraniectomy (DHC) in patients with aneurysmal subarachnoid haemorrhage (SAH) with regard to infarction, haemorrhage or brain swelling. METHODS: DHC was performed in 43 of 787 patients with SAH. Patients were stratified according to (1) primary brain swelling without and (2) with additional intracerebral haematoma, (3) secondary brain swelling without rebleeding or infarcts and (4) with infarcts or (5) with rebleeding. Outcome was assessed according to the modified Rankin scale at 6 months RESULTS: Overall, 36 of 43 patients (83.7%) with DHC and 241 of 744 patients (32.4%) without DHC have been of a poor grade on admission (World Federation of Neurological Societies grading 4-5; p<0.0001). Favourable outcome was achieved in 11 of 43 (25.6%) patients with DHC. There was no difference in favourable outcome after primary (25%) versus secondary (26.1%) DHC (p = 1.0). Subgroup analysis (brain swelling vs bleeding vs infarcts) revealed no difference in the rate of favourable outcome. In a multivariate analysis, acute hydrocephalus (p = 0.02) and clinical herniation (p = 0.03) were significantly associated with unfavourable outcome. CONCLUSIONS: We conclude that primary and secondary hemicraniectomy may be warranted, irrespective of the underlying aetiology-infarction, haemorrhage or brain swelling. The time from onset of intractable ICP to DHC seems to be crucial, rather than the time from SAH to DHC.

Significance of serial S100b and NSE serum measurements in surgically treated patients with spondylotic cervical myelopathy.

BACKGROUND: Predicting functional outcome following surgery performed for spinal cord compression is still a considerable problem. Recent observations, though, strongly suggest that with serial measurements of serum S100b, this might be possible in patients with subacute spinal cord compression. The aim of this study was to examine whether this potential significance of S100b applies as well to patients with spondylotic cervical myelopathy. A further purpose was to assess the value of NSE in this regard, another biochemical marker widely used to monitor cerebral lesions. METHODS: Fifty-one patients were included in this prospective study. Outcome was considered as favourable in case of neurological improvement with preservation or retrieval of walking ability, whereas non-improvement without restoration of gait function was regarded as unfavourable. The preoperative levels of S100b and NSE were correlated with the degree of paresis, duration of symptoms, and presence of intramedullary high signal intensities on MRI. The postoperative values of both markers were correlated with outcome. FINDINGS: The preoperative levels of S100b were neither correlated with degree or duration of paresis nor with outcome. In case of an uncomplicated course the postoperative levels of S100b were also not correlated with outcome. In complicated courses with acute postoperative deterioration normal values on the 3rd day after the event were associated with a favourable outcome, whereas one patient with unfavourable outcome showed a persistent pathological increase. The serum levels of NSE were not correlated with clinical parameters or with outcome in any of the cases. CONCLUSIONS: Serial S100b serum measurements do not permit prediction of functional outcome in patients with spondylotic cervical myelopathy in case of an uncomplicated postoperative course. In complicated courses with postoperative deterioration, such measurements reflect postoperative events with possibly prognostic relevance. NSE does not have any significance in these patients with chronic lesions of the spinal cord.

Plant-derived triterpenoids as potential antineoplastic agents.

Man has relied on plants as a source of medicinal agents for centuries. Today, with the specter of antibiotic resistance, emerging infectious diseases, and cancers, phytochemicals continue to provide new structural leads for the chemotherapeutic industry. A number of triterpenoids have shown promise as antineoplastic agents. Members of the cycloartane, lupane, ursane, oleanane, friedelane (especially quinone methides), dammarane, cucurbitacin, and limonoid triterpenoids, have demonstrated anti-proliferative activity on various cancer cell lines. This review covers the recent developments regarding antineoplastic/cytotoxic triterpenoids, excluding saponins, from higher plants.

Differential expression of calbindin and calretinin in the human fetal amygdala.

The distribution patterns of the calcium-binding proteins calbindin and calretinin, both expressed early during development within the various amygdaloid nuclei and areas, have been investigated. Anti-calbindin as well as anti-calretinin mark immature, partly migrating neurons in the 5th gestational month; the number of calretinin-immunoreactive neurons is distinctly higher. In the 8th month, calbindin and calretinin are found in a small proportion of presumed pyramidal cells and in various types of non-pyramidal neurons. Small and large bipolar and small and large multipolar neurons are shown to express calbindin and calretinin. Double-labellings show that calbindin and calretinin are largely contained in different subsets of these neuronal types, which are considered to represent interneurons. These nerve cell classes are widespread within the amygdala with mainly moderate to high packing densities. Diffuse immunoreactive structures, which are found in different intensities in the various amygdaloid nuclei, display distinct redistribution during fetal development. The results show that during early fetal development calbindin and particularly calretinin may be involved in the regulation of neuronal migration. In later development, definite subsets of interneurons, which are likely to be functionally different, are marked by anti-calbindin and -calretinin. Different diffuse immunolabelling at various developmental stages probably indicates the sequential arrival of afferent input from brain areas containing calbindin- or calretinin-immunoreactive nerve cells. With the exception that calretinin may be transiently expressed in pyramidal neurons, the distribution of calbindin- and calretinin-immunoreactive structures to a large degree corresponds to that in the adult. Thus, little reorganisation is to be expected during proceeding development.

Expression of a kinase anchoring protein 79 in the human fetal amygdala.

The expression of AKAP (a kinase anchoring protein) 79 enriched in postsynaptic densities has been investigated in the human amygdaloid nuclei of the 8th gestational month. Nuclear specific diffuse and cellular immunostaining is observed. An outstanding feature of cellular immunostaining is the labelling of somata and dendritic trees in a manner that allows neuronal classification. Bipolar, multipolar, and pyramidal AKAP79-positive neurons are found throughout the amygdala; the highest packing density of immunostained neurons is seen within the central and lateral nucleus. Dense diffuse immunolabelling is observed in the lateral and accessory basal nucleus. The results indicate that AKAP79 is expressed in various neuronal types (projection as well as local circuit neurons). Diffuse staining does not always match with cellular labelling within a nucleus, thus, AKAP79 may be particularly enriched in dendrites in some nuclei. The widespread distribution of AKAP79 indicates its possible role in various amygdaloid circuitries; thus, AKAP79 does not seem to be restricted to definite functional systems in the 8th month.

Distribution of SNAP-25 in transient neuronal circuitries of the developing human forebrain.

The distribution of SNAP-25 is demonstrated within prominent transient structures in the developing human forebrain. During early fetal development SNAP-25 is mainly expressed in axons of the intermediate zone and the internal capsule. The fibers appear directed towards the mantle zone of the ganglionic eminence and the perireticular nucleus located within the internal capsule. Cells of these two areas are shown to interact with SNAP-25 immunoreactive structures with the aid of double-labellings. The SNAP-25 immunoreactive fibers may represent corticofugal axons which contact the perireticular nucleus and ganglionic eminence which are regarded as intermediate targets providing a scaffold for growing axons. Anti-SNAP-25, thus, is an appropriate marker of intermediate targets which are involved in brain injuries of preterm infants.

Expression of MAP1a and MAP1b in the ganglionic eminence and the internal capsule of the human fetal brain.

The expression of microtubule-associated proteins 1a and 1b (MAP1a and 1b) were investigated in two transient structures, the ganglionic eminence (GE) being a prominent part of the telencephalic proliferative zone and the perireticular nucleus (PR) within the internal capsule (IC). Anti-MAP1a immunolabels PR neurons from 18 weeks of gestation (wg) onwards, whereas anti-MAP1b immunolabels long IC fibers between 18 and 22 wg. MAP1b is further present in thalamic fibers that seem to terminate at the medial margin of the GE, in a moderate number of cells of the GE and its medial extension, the gangliothalamic body (GTB). From 26 to 33 wg MAP1b is expressed in short fiber bundles of the IC, a few MAP1b-positive cells are seen in the GE. MAP1a has so far been described to appear in differentiated neurons and to be related to late developmental events. However, the transient PR being involved in axonal guidance as an intermediate target shows a precocious MAP1a-expression. The MAP1b-finding that thalamocortical fibers accumulate at the GE-margin indicates that this region represents an intermediate target for these fibers. The short MAP1b fiber bundles found in the IC are in accordance with cell culture experiments showing that MAP1b is concentrated in distal parts of outgrowing axons.

Distribution of GAP-43-immunoreactive structures in the human fetal amygdala.

The growth-associated protein GAP-43 is a developmentally regulated protein which is involved in the formation of neuronal contacts. In immunohistochemical studies, GAP-43 is detected within axons during their elongation; thus a fibrous immunoreactivity is visible. After axonal growth is completed there is a shift from a fibrous to a punctate immunoreactivity. The latter has been shown to correlate with synaptogenesis. In the amygdala of the 5th gestational month, a fibrous GAP-43-immunoreactivity is seen in the basolateral nuclei, whereas the corticomedial nuclei exclusively show a punctate immunoreactivity. In the 7th month, all amygdaloid nuclei display immunoreactive puncta, but no fibers. In the 9th month GAP-43-immunoreactivity is no longer visible within the amygdala. The results demonstrate the differential distribution of GAP-43-immunoreactive structures in the amygdaloid nuclei. The nuclear specific immunostaining and its changes may indicate the sequential appearance of the monoaminergic innervation of the amygdala, as GAP-43 is known to occur in monoaminergic systems. Nuclei involved in high levels of the cortical processing hierarchy such as the lateral or basal nucleus display a late occurrence of GAP-43-immunoreactivity. In general, anti-GAP-43 has been shown to be an appropriate tool to investigate axonal growth and synaptogenesis in the developing human brain.

Diagnostic impact of proton MR-spectroscopy versus image-guided stereotactic biopsy.

BACKGROUND: The aim of this study was to compare the diagnostic accuracy of (1)H MR-spectroscopy versus image-guided stereotactic biopsy. METHOD: A cohort of 83 consecutive patients with a broad spectrum of brain lesions were examined. Prior to stereotactic biopsy, the patients were subjected to (1)H MR-spectroscopy examination. Diagnostic accuracy of (1)H MR-spectroscopy and image guided stereotactic biopsy was determined for the largest diagnostic subgroups. Each diagnostic procedure was tested for concordance in every subgroup. FINDINGS: The subgroups of patients comprised: low grade glioma, high grade glioma (grades III and IV), lymphoma and metastasis. For the sensitivity of (1)H MR-spectroscopy ranged from 87.7 in high grade glioma to 92.3% in metastasis and for specificity from 93.3% for high grade glioma to 100% in low grade glioma. The highest positive predictive value of 100% was reached in the subgroup of low grade glioma. The highest negative predictive value was reached in lymphoma and metastasis, 100%. The kappa values were highly significant for all comparisons (p<0.001). The co-efficient ranged from 0.68 to 0.84. It was lowest in assessing high grade glioma and highest in lymphoma. CONCLUSION: Compared with each other (1)H MR-spectroscopy and image-guided stereotactic biopsy showed a moderate to good, statistically highly significant concordance. In patients in whom operation is at an increased risk e.g., due to severe medical illness, (1)H MR-spectroscopy as a noninvasive procedure may be sufficient to assess the diagnosis.

Protein S-100b as serum marker for prediction of functional outcome in metastatic spinal cord compression.

BACKGROUND: To evaluate the significance of protein S-100b as a serum marker for the prediction of functional outcome in the event of symptomatic spinal cord compression due to epidural metastases. METHOD: 34 patients with paresis due to metastatic spinal cord compression were included in this prospective study. Venous blood samples for protein S-100b were taken after admission and regularly after operative decompression. The individual time course of protein S-100b levels was correlated with the clinical outcome by means of motor function. Outcome was considered to be favourable in case of neurological improvement and preservation or retrieval of walking ability whereas non-improvement or further neurological deterioration without restoration of function of ambulation was regarded to be unfavourable. FINDINGS: Patients with favourable outcome had serum levels of S-100b which were either normal all the time or which were initially increased but normalised within 2 to 3 days. Patients with unfavourable outcome, however, had increased levels throughout which showed either a further increase or only a slow decrease within approximately two weeks (p=0.0001). INTERPRETATION: These preliminary results suggest that, analogous to cerebral disorders, protein S-100b might be a promising serum marker to predict functional outcome in symptomatic spinal cord compression.

Transient architectonic features in the basolateral amygdala of the human fetal brain.

The architectonical differentiation in the basolateral nuclei of the human fetal amygdala - with special reference to transient structures - was studied using series of relatively thick Nissl-stained sections. These architectonic features were correlated with the process of migration. Radial glial fibers providing the scaffold of migratory routes can reliably be marked with the aid of antivimentin. In the 5th gestational month a transient feature is conspicuous in the inferior portions of the basolateral nuclei bordering upon the ganglionic eminence (proliferative zone): columnar cell clusters, separated by cell-sparse septa, extend from the poliferative zone to the nuclei. The width of the cell columns vary considerably between the different nuclei. In vimentin immunopreparations fibers are found inside these cell columns. So they most probably reflect clustered migratory streams. Two months later, instead of this merging area between the ganglionic eminence and the amygdaloid nuclei a cell-free capsule envelopes the nuclei and clearly separates them from the ganglionic eminence. Changes in cytoarchitectonics are accompanied by a distinct rearrangement of radial glial fibers. A basket-like arrangement of the vimentin-immunoreactive fibers around the cell columns inside the cell sparse septa is found. Towards the end of pregnancy radial glial fibers gradually vanish. A comparison of Nissl and vimentin preparations reveals that transient architectonic characteristics as visible in relatively thick Nissl sections may be correlated with migrational routes.

Delayed hydrocephalus after resection of supratentorial malignant gliomas.

BACKGROUND: To report our experience with 12 patients who developed delayed hydrocephalus after resection of supratentorial malignant gliomas. METHOD: The charts of all affected patients were analysed retrospectively for clinical presentation, time interval between initial operation and occurrence of hydrocephalus, neuroradiological findings, constituents of cerebrospinal fluid (CSF), surgical treatment, and outcome. FINDINGS: After initial good recovery following tumour resection all patients deteriorated secondarily due to development of hydrocephalus which was not encountered in the first postoperative CT-scans. Incidence is 3.4% overall and is 8.3% if exclusively calculated for frontal gliomas but increases to 15.2% if specified for patients with ventricular entry during tumour resection. Development of hydrocephalus is suggested to be due to proteinic precipitation since analysis of CSF revealed marked elevation of proteins in all patients. Whereas shunting of mere hydrocephalus yields satisfactory results outcome in cases of multiloculated hydrocephalus necessitating placement of multiple catheters is questionable. INTERPRETATION: Development of hydrocephalus after resection of malignant gliomas is not rare. It should be considered in patients with delayed deterioration after initial improvement. Outcome in relation to hydrocephalus is favourable in cases of mere communicating hydrocephalus, occurrence of multiloculated hydrocephalus, however, heralds a poor prognosis.

Severe intracranial bleeding mimicking acute inferior myocardial infarction with right ventricular involvement.

Electrocardiographic (ECG) changes and wall motion abnormalities of the left ventricle have been observed in patients with severe intracranial hemorrhage. However, ECG evidence of an acute myocardial infarction in this setting is extremely rare but may have important therapeutic consequences. We report the case of a 45-year-old female who became unconscious with respiratory insufficiency after an endoscopic retrograde cholangiopancreaticoscopy with ECG changes consistent of an inferior myocardial infarction with right ventricular involvement. Immediate coronary angiography revealed normal coronaries; however, left ventricular angiography showed extensive wall motion abnormalities predominantly in the anteroseptal region. Immediate cranial computer tomography demonstrated massive intracranial bleeding. Intracranial hemorrhage can be associated in the initial phase with ECG evidence of an acute myocardial infarction. This has to be taken into consideration in the setting of unexplained loss of consciousness or nonresponsiveness of a patient. A rapid diagnostic evaluation has to be initiated to rule out a myocardial infarction and to diagnose intracranial hemorrhage before the use of thrombolytic or anticoagulant therapy.

Changing distribution patterns of synaptophysin-immunoreactive structures in the human dorsal striatum of the fetal brain.

Within the striatum two compartments, matrix and patches, can be distinguished by differences in the expression of neuroactive substances, afferent and efferent connections and time of neurogenesis. The present study was done to demonstrate the pattern of synaptophysin (SYN) expression which is indicative of synaptogenesis in the human fetal striatum (15th-32nd weeks of gestation) with special reference to developmental changes. From the 15th to the 22nd gestational weeks an intense diffuse SYN immunolabelling of striatal patches is observed. In the matrix SYN-immunoreactive fiber bundles are seen until the 20th week. Thereafter, the matrix is nearly devoid of SYN-immunoreactive structures. From the 28th week of gestation the matrix contains diffuse SYN immunoreactivity which gradually becomes as intense as that of the patches. The latter, thus, can no longer be delineated in the 30th week. The results show that fibrous SYN immunolabelling most probably indicating intra-axonal transport of synaptic vesicles can only be observed during the first half of gestation. Moreover, it becomes obvious that the patch compartment can selectively be visualized by anti-SYN until the 28th week. This pattern may correspond to the early dopaminergic innervation from the substantia nigra which is known to reach the developing patches. From the 28th week a transition from patchy to diffuse immunolabelling is seen. The increase in matrix labelling may be due to the occurrence of new neuronal contacts. The changeover from patchy to homogeneous SYN immunolabelling takes place distinctly earlier than changes in the distribution of other neuroactive substances described before.

Biologically active triterpenoids of Syncarpia glomulifera bark extract from Paluma, north Queensland, Australia.

The crude chloroform bark extract of Syncarpia glomulifera (Myrtaceae) shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of oleanolic acid-3-acetate, ursolic acid-3-acetate and betulinic acid. The relatively large abundance (10% of the crude extract) and high degree of activity of betulinic acid are responsible for the bioactivity of the crude bark extract.

Severe delayed diffuse cerebral vasospasm and cerebral infarctions following spinal subdural hemorrhage.

BACKGROUND: We report a rare case of severe delayed cerebral vasospasm with cerebral infarctions after spinal subdural hemorrhage. CASE REPORT: A 56-year-old woman presented with an acute onset of paraplegia. MR-imaging revealed an extensive intraspinal hemorrhage reaching from T1 to L1. The hematoma was evacuated via a T8-laminectomy. At the 7th postoperative day the patient developed visual disturbances. MR-scanning revealed extensive infarctions and cerebral angiography showed severe diffuse vasospasms. INTERPRETATION: This case demonstrates that cerebral vasospasm may be caused by a spinal subdural hemorrhage, supporting the hypothesis that cerebral vasospasm may be triggered by factors from a remote site and that a direct contact of blood clots with the vessel is not mandatory.

Synthesis and cytotoxic activity of a series of diacetylenic compounds related to falcarindiol.

The synthesis of a series of diacetylenic compounds related to the natural product falcarindiol has been carried out. Unsymmetrical diacetylenes were prepared by a modification of the Cadiot-Chodkiewicz coupling reaction, while a Glaser coupling was used to prepare symmetrical diacetylenes. These compounds have been tested for in vitro cytotoxic activity against Hep-G2, and H-4-II-E cell lines. Diacetylenes with additional unsaturation at C-1, 2, appended with hydroxyl groups at C-3 and C-8, or with long hydrophobic chains, exhibited IC50 values in the micromolar range.

Biological activity of the essential oil of Myrcianthes sp. nov. "black fruit" from Monteverde, Costa Rica.

The leaf essential oil of an undescribed species of Myrcianthes has been obtained from Monteverde, Costa Rica. The essential oil exhibits in vitro cytotoxic activity against Hep-G2 and SK-Mel-28 human tumor cell lines. A GC/MS analysis shows the essential oil to be composed of 2-heptanol, alpha-pinene, beta-pinene, limonene, cineole, and alpha-terpineol, alpha-Pinene, beta-pinene, and limonene account for the cytotoxic activity of the leaf essential oil of Myrcianthes sp. nov. "black fruit".

Isoterchebulin and 4,6-O-isoterchebuloyl-D-glucose, novel hydrolyzable tannins from Terminalia macroptera.

Two new hydrolyzable tannins, isoterchebulin (1) and 4,6-O-isoterchebuloyl-D-glucose (2), together with six known tannins, 3-8, were isolated from the bark of Terminalia macroptera. Their structures were elucidated by extensive 1D and 2D NMR studies, MS, and chemical transformations. Biological activities of all compounds were evaluated against the snail Biomphalaria glabrata, the bacteria Bacillus subtilis and Pseudomonas fluorescens, the nematode Caenorhabditis elegans, and four cancer cell lines (Hep G2, MCF-7/S, MDA-MB-231, and 5637 cells). All compounds except 3 showed antimicrobial activities against B. subtilis (MIC 8-64 microg/mL), whereas only 1 was active against C. elegans (100 microg/mL) and B. glabrata(LC(100) = 60 microg/mL). 3 and 8 were toxic against 5637 cells with LC(50) = 84.66 and 41.40 microM, respectively.