Bare, bio-active and hydrogel-coated coils for endovascular treatment of experimentally induced aneurysms. Long-term histological and scanning electron microscopy results.

Endovascular treatments of cerebral aneurysms with bare platinum coils have a higher rate of recurrence compared to surgical clipping. This may be related to failed vessel wall reconstruction since histological and scanning electron microscopy results following embolization failed to demonstrate neoendothelialization over the aneurysm neck. The present study tried to elucidate whether the use of modified coils resulted in a better rate of reconstructing the vessel wall over the aneurysm neck in experimental aneurysms. Aneurysms were created in 20 rabbits by intraluminal elastase incubation of the common carotid artery. Five animals each were assigned to the following groups: untreated, bare platinum coils, bioactive coils with polyglycolic/polylactic acid coating, and hydrogel-coated platinum coils. After 12 months, angiography, histology and scanning electron microscopy was performed. No neoendothelial layer was visualized in the bioactive and bare coil groups with a tendency to an increased layering of fibroblasts along the bioactive coils at the aneurysm fundus. However, at the aneurysm neck perfused clefts were present and although a thin fibrinous layer was present over some coils, no bridging neointimal or neoendothial layer was noted over different coils. Following loose Hydrogel coiling, a complete obliteration of the aneurysm was present with neoendothelialization present over different coil loops. The study demonstrates that with surface coil modifications complete and stable aneurysm obliteration may become possible. A smooth and dense surface over the aneurysm neck may be necessary for endothelial cells to bridge the aneurysm neck and to lead to vessel wall reconstruction.

Evaluation of tissue components in the peripheral nervous system using Sirius red staining and immunohistochemistry: a comparative study (human, pig, rat).

Little is known about species differences in the peripheral nerve system and quantitative evaluation of main tissue components has rarely been done. Nevertheless, animal models are used for example in pain research without exact knowledge of degree of fibrosis in pathological states which would determine possible treatment options. It would therefore be of crucial interest to describe the degree of fibrosis and the remaining functional nerve tissue as exact as possible. In the present study we evaluated collagen (stroma) and nerve fiber (parenchyma) composition of peripheral nerves in three species (human, rat, pig) and used digital colour-separation and analysis for collagen type differentiation and quantification of immuno-positive-stained area. We found similar ratios of collagen types I and III in epineurium and similar immuno-positive area for staining of neurofilament and S-100beta. In contrast, we measured significantly different ratios of collagen type I to type III in the endoneurium. This combined analysis of the main tissue components of peripheral nerves could be an easy-to-use tool in evaluating changes during damage caused by scaring, systemic disease or compression syndromes. The calculated collagen type I/III ratio may serve as an objective diagnostic value for the description or as prognostic marker for therapeutic approaches in peripheral nerve pathology. However, in particular studies of collagen accumulation in nerves, species dependant differences have to be considered.

[Different manifestations of the cerebral nocardiosis]. / Unterschiedliche Manifestationsformen der zerebralen Nokardiose.

Nocardial infections affect mainly the respiratory tract but also can attack the CNS. Clinical experience with cerebral nocardiosis is very limited. We present two patients with very different cerebral affections due to nocardiosis. Cerebral nocardial infections can cause both multiple small abscesses and single large abscesses in the human brain. Despite the rare incidence of cerebral nocardiosis, it is an important differential diagnosis of expansive processes and abscesses in the CNS.

Technical pitfalls in a porcine brain retraction model. The impact of brain spatula on the retracted brain tissue in a porcine model: a feasibility study and its technical pitfalls.

We describe technical pitfalls of a porcine brain injury model for identifying primary and secondary pathological sequelae following brain retraction by brain spatula. In 16 anaesthetised male pigs, the right frontal brain was retracted in the interhemispheric fissure by a brain spatulum with varying pressures applied by the gravitational force of weights from 10 to 70 g for a duration of 30 min. The retracted brain tissue was monitored for changes in intracranial pressure and perfusion of the cortex using a Laser Doppler Perfusion Imager (MoorLDI). To evaluate the extent of oedema and cortical contusions, MRI was performed 30 min and 72 h after brain retraction. Following the MR scan, the retracted brain areas were histopathologically assessed using H&E and Fluoro-Jade B staining for neuronal damage. Sinus occlusion occurred in four animals, resulting in bilateral cortical contusions and extensive brain oedema. Retracting the brain with weights of 70 g (n = 4) caused extensive oedema on FLAIR images that correlated clinically with a hemiparesis in three animals. Morphologically, an increased number of Fluoro-Jade B-positive neurons were found. A sequential decrease in weights prevented functional deficits in animals. A retraction pressure applied by 10-g weights (n = 7) caused a mean rise in intracranial pressure to 4.0 +/- 3.1 mm Hg, and a decrement in mean cortical perfusion from 740.8 +/- 41.5 to 693.8 +/- 72.4 PU/cm2 (P < 0.24). A meticulous dissection of the interhemispheric fissure and a reduction of weights to 10 g were found to be mandatory to study the cortical impact caused by brain spatula reproducibly.

[Infectious mononucleosis]. / Die infektiöse Mononukleose.

The primary infection with Epstein-Barr virus in an immunocompetent individual leads to infectious mononucleosis with symptoms of diphtheroid angina, lymph node swelling in the neck and hepatosplenomegaly. The most common age of infection lies between 15 and 25 years. The illness can affect a number of organs simultaneously and thus requires interdisciplinary diagnostics. For differential diagnosis, a differential blood analysis and a EBV quick test are required. The presence of IgM antibodies demonstrates the presence of the infection. Ultrasound of the abdomen can be made to determine the involvement of additional organs. In most cases, recovery occurs without complications. Acute cases can usually be handled successfully with medication. If symptomatic treatment fails, pharyngeal airway obstruction is possible and a tonsillectomy may be necessary. Otherwise, surgical treatment is obsolete. Generally, the prognosis is good. Severe courses and complications are rare.

Expression pattern of NOGO-A protein in the human nervous system.

The distribution pattern of NOGO-A protein, an important axon growth inhibitory molecule and member of the reticulon family, has been investigated in the adult human brain, spinal cord, retina and dorsal root ganglia. Intense NOGO-A immunoreactivity was detected in oligodendroglial cell bodies and their myelin sheaths in nerve fibre tracts of the central nervous system. Furthermore, numerous populations of neurons in the brain and spinal cord expressed NOGO-A to a variable extent in their cell bodies and neurites, suggesting additional, as-yet-unknown, functions of this protein.

[Diagnosis of an initial infratentorial central nervous system B-cell lymphoma during prolonged cortisone medication]. / Diagnose eines initial infratentoriellen primären B-Zell-Lymphoms des ZNS unter prolongierter Kortisonmedikation.

We present a patient with primary central nervous system B-cell lymphoma. He had suffered from slowly developing weight loss and presented to us with disorientation, seizures, and a supranuclear gaze disturbance. The patient was dismissed with the primary diagnosis of autoimmune encephalitis of the brainstem and put on oral corticosteroids. Four months later, his health status had deteriorated, and at that time diagnostic methods pointed to a cerebral lymphoma. Stereotactic biopsy with subsequent immunohistochemistry and polymerase chain reaction analysis revealed a highly malignant B-cell lymphoma of the CNS, despite prolonged corticosteroid treatment. The patient was treated with whole brain radiotherapy.

[Spinal cord compression by a cervical oseteocartilaginous exostosis: surgical strategy aspects]. / Rückenmarkskompression durch eine zervikale osteokartilaginäre Exostose: Operationsstrategische Aspekte.

AIM: The authors present the therapeutic management of a 12-year-old boy with known hereditary multiple exostosis syndrome (HME), who developed spinal cord compression symptoms caused by an exostosis of the C2 lamina. A perinatal brain lesion with tetraparesis delayed the recognition of the spinal cord compression substantially, which resulted in an extensive spur-like growth of the exostosis. METHOD: In comparison with already published cases, this growth pattern was rather unique and required consideration on the best surgical management. We decided to monitor the spinal cord function from positioning of the patient to skin closure and to modify the surgical steps of the laminectomy with initial lateral cutting of both hemilaminae. RESULTS: Electrophysiological monitoring helped to avoid spinal cord compression by inadequate head anteflexion during positioning. Lateral cutting of the hemilaminae C2 resulted in spontaneous extrusion of the exostosis with immediate improvement of the electrophysiological findings. The boy experienced a prompt improvement of his neurological deficits. CONCLUSION: The good surgical and clinical result confirm the value of the applied management concept.

A case of gliosarcoma appearing as ischaemic stroke.

OBJECTIVES: Ischaemic stroke attributable to malignant brain tumour is a rarely reported phenomenon and even various imaging techniques including angiography do not necessarily lead to an accurate diagnosis. CASE DESCRIPTION: A 46-year-old, previously healthy man developed apoplectic symptoms with slight right sided hemiparesis and global aphasia. The computed tomography (CT) scan showed lesions of the left temporal lobe and the paraventricular white matter suggestive of left middle cerebral artery (MCA) infarction. Carotid angiography demonstrated compression of the M1 segment of the MCA and occlusion of temporal MCA. The patient initially refused magnetic resonance imaging (MRI) because of claustrophobia. Because of fluctuating symptoms and successive worsening of the condition over weeks an MRI scan was conducted under general anaesthesia. Beneath temporal, opercular, and subcortical infarctions it revealed a left temporal tumour. A tumour biopsy disclosed a gliosarcoma (WHO grade IV). Microscopical examination of the surgical specimen demonstrated invasion of tumour cells into the wall of a greater pre-existing blood vessel. CONCLUSIONS: Malignant brain tumours may cause ischaemic infarction. This is a rare but important differential diagnosis for the origin of strokes. The authors describe the first case with infiltration of intracranial blood vessels by tumour cells of a gliosarcoma.

[Rhabdomyolysis following cerivastatin monotherapy--implications for therapy with HMG-CoA reductase inhibitors]. / Rhabdomyolyse unter Cerivastatin-Monotherapie. Konsequenzen für die Therapie mit HMG-CoA-Reduktase-Hemmern?

Cerivastatine was administered as a reversible HMG-CoA reductase inhibitor (statine) to treat hypercholesterolemia until its withdrawal from the market following 52 reports of death due to drug-related rhabdomyolysis and acute renal failure. In most cases, cerivastatine was applied in combination with drugs which influenced the liver metabolism of cerivastatine via cytochromeoxidase P 450 isoenzymes. We report a well-documented case of acute rhabdomyolysis following cerivastatine monotherapy. The diagnosis was confirmed additionally by muscle biopsy.Finally,we give an overview of the current knowledge concerning therapy with HMG-CoA reductase inhibitors,1 year after the withdrawal of cerivastatine from the market.

Recurrent focal myositis of the peroneal muscles.

Recurrent focal myositis is a rare entity and can be difficult to diagnose and treat. A long-term follow-up and diagnostic evaluation was carried out in a patient who presented with ankle stiffness secondary to a painful mass within the calf. This process was diagnosed as focal myositis of the peroneal muscles, which recurred over a period of 7 yr. A review of the literature regarding focal myositis, treatment options and a successful conservative therapy regimen, as an alternative to a surgical protocol, are presented. After making the diagnosis with the help of a muscle biopsy, long-term therapy should be considered. Conservative treatment of focal myositis with anti-inflammatory drugs and physical therapy can be successful but recurrence may occur if the medical treatment is interrupted.

Acute onset of hemorrhagic leukoencephalomyelitis (Hurst) in the spinal cord.

Acute hemorrhagic leukoencephalomyelitis is considered to be a rare autoimmune disorder. The present case, a 34-year-old male, developed non-specific symptoms 3 weeks after surgical removal of his meniscus and following an inconspicuous infection of the upper respiratory tract. The spinal cord was the first to be affected, followed by symptoms of headache, nausea and fever which reached 39.4 degrees C. Autopsy revealed acute hemorrhagic leukoencephalomyelitis with marked involvement of the spinal cord. Diagnosis was established by histopathological examination of the brain and spinal cord. This is the first description of the onset of this disease in the spinal cord.

Experimental MR imaging-guided interstitial cryotherapy of the brain.

BACKGROUND AND PURPOSE: Hyperthermal ablation techniques such as laser or RF ablation require dedicated heat-sensitive MR imaging sequences for monitoring MR imaging--guided interventions. Because cryotherapy does not have these limitations, the purpose of this study was to evaluate the feasibility of MR imaging--guided percutaneous cryotherapy of the brain. METHODS: An experimental cryoprobe with an outer diameter of 2.7 mm was inserted into the right frontal lobe of 11 healthy pigs under MR imaging control. Freezing procedures were monitored by using an interventional 1.5-T magnet and a gradient-echo sequence with radial k-space trajectories, a fast T2-weighted single-shot spin-echo sequence, and a T1-weighted single-shot gradient-echo sequence. In three animals, the procedure was also monitored by using dynamic CT. A freeze-thaw cycle with a duration of 3 minutes was repeated three times per animal. Follow-up MR images were obtained 3, 7, and 14 days after cryotherapy by using conventional MR sequences. Six animals were killed 7 days after intervention, and five animals were killed 14 days after intervention. The brains were sectioned, and the histologic findings of the lesions were compared with the MR imaging appearance. RESULTS: No artifacts due to the probe were observed on the MR images or CT scans. The ice formation (mean diameter, 12.5 mm) was very well delineated as a signal-free sphere. MR monitoring of the freezing procedure yielded a significantly higher ice:tissue contrast than did CT. The size of the ice ball as imaged by MR imaging and CT during the intervention correlated well with the MR imaging appearance of the lesions at the 14-day follow-up examination and with the histologic findings. Histologically, coagulation necrosis and gliosis were found, surrounded by a transition zone of edema and a disrupted blood-brain barrier, corresponding to a contrast-enhancing rim around the lesions on follow-up MR images. CONCLUSION: MR imaging-guided cryotherapy of the brain is possible and allows a precise prediction of the resulting necrosis. MR imaging of the freezing process does not require heat-sensitive sequences and is superior to CT for monitoring of cryoablation.

MR-guided percutaneous cryotherapy of the liver: in vivo evaluation with histologic correlation in an animal model.

The purpose of this study was to evaluate the feasibility of MR-guided percutaneous cryotherapy of the porcine liver and to correlate the resulting tissue necrosis with MR imaging and histology. Using an MR-compatible, argon-based cryotherapy system (CryoHit; Galil Medical Ltd., Israel) with 2- and 3-mm diameter tapered cryotherapy probes, MR-guided percutaneous cryotherapy was performed in seven pigs (mean body weight, 40 kg) under general anesthesia in a short-bore magnet (1.5 T ACS NT; Philips, The Netherlands) using an ultrafast T2-weighted single-shot LoLo TSE sequence and a T1-weighted gradient-echo sequence. The frozen liver tissue was depicted accurately on fast T2- and T1-weighted sequences, providing precise delineation of the ablated tissue volume. On follow-up postcontrast MR controls, the cryolesions appeared avascular. They decreased in size compared with the initially frozen volume down to 70% at a 2-week follow-up. Histologically, a coagulation necrosis with a close correlation to the MR follow-up examinations was objectified. No cryotherapy-related complications occurred. J. Magn. Reson. Imaging 2001;13:50-56.

Effects of ascorbic acid on retinal pigment epithelial cells.

PURPOSE: Evaluation of effects of ascorbic acid on cell characteristics of dedifferentiated porcine retinal pigment epithelial (pRPE) cells. METHODS: pRPE cells were incubated in vitro with increasing concentrations of ascorbic acid (0.25-1.5 mMol). Cell proliferation was assayed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BrdU) into cellular DNA. Migration and contraction properties were studied on a cell permissive porous membrane and collagen gels, respectively. Phenotypic changes in response to ascorbic acid and its derivative ascorbic acid 2-phophate were evaluated by microscopy and indirect immunofluorescence. RESULTS: Ascorbic acid significantly inhibits cell proliferation, migration, and contraction in concentrations of 1 mMol or more. Under the influence of at least 1 mMol ascorbic acid dedifferentiated pRPE cells exhibited a pigmented status within 24 hours. Addition of 500 U/ml catalase prevented the antiproliferative effect of ascorbic acid and the formation of pigment. Concentrations of 0.5 mMol ascorbic acid as well as 1 mMol ascorbic acid 2-phosphate promoted differentiation of cell phenotype. Furthermore, ascorbic acid 2-phosphate supported the formation of in vivo-like epithelial structures. CONCLUSIONS: Ascorbic acid has an influence on vital cell characteristics such as proliferation, migration, contraction and differentiation of pRPE cells. As dedifferentiation of these cells is an integral part in the development of proliferative vitreoretinopathy (PVR), ascorbic acid should be taken into consideration as a supplement in the clinical management of this disease.

Expression of heat shock proteins 72/73 in human peritoneal mesothelial cells in vivo and in vitro.

Leukocyte accumulation during peritonitis leads to an injurious microenvironment which is involved in the host defense reaction but is also thought to cause peritoneal damage. We tested the hypothesis that mesothelial cells (MC) respond to the injurious microenvironment during peritonitis by an increased expression of heat shock proteins (HSP 72/73), a basic way by which cells are protected against injury. Comparison of resting MC and activated MC during peritonitis in vivo by means of immunohistochemistry revealed an increased expression of HSP 72/73. As assessed by Western immunoblotting, incubation of MC in vitro with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) caused a time-dependent induction of HSP 72/73 expression, which was maximal 6 h after stimulation. We suggest that the increased HSP 72/73 expression of MC during peritonitis is in part induced by TNF-alpha and IL-1beta and may exert a cell-protective function, lessening MC damage during peritonitis.

[Results of pretherapeutic lymph node diagnosis in head and neck tumors. Clinical value of 18-FDG positron emission tomography (PET)]. / Ergebnisse der prätherapeutischen Lymphknotendiagnostik bei Kopf-Hals-Tumoren. Klinische Wertigkeit der 18FDG-Positronen-Emissions-Tomographie (PET).

BACKGROUND: Histological studies demonstrate that there is a high percentage of occult nodal metastasis in head and neck malignomas. Patients with positive lymph nodes have a comparatively worse prognosis. A neck dissection is required in these cases. By demonstrating morphological abnormalities, imaging procedures like ultrasound, computer tomography (CT), and magnetic resonance imaging (MRI) can provide important initial informations about possible malignant alteration of the lymph nodes. Positron emission tomography (PET) allows functional metabolic imaging of a suspected tumor site. The aim of this study was a comparative evaluation of different diagnostic procedures with special emphasis on the value of PET in the pretherapeutic diagnosis of nodal spread in head and neck cancer. PATIENTS AND METHODS: Forty patients (28 male and 12 female) with a suspected malignoma in the head and neck region underwent clinical examination including palpation of the neck sides, ultrasound, CT, and PET to detect a nodal spread of the malignancy. Fifty neck dissections were performed in 28 patients. Lymph node biopsies were performed in the remaining patients. The results of the diagnostic procedures were compared to the histology and the clinical course of the patients. The mean follow-up period was 12.5 months. RESULTS: A nodal metastasis was verified in 35% of all cases. Sensitivity of all imaging procedures including PET was 82%. Palpation had a sensitivity of only 61%. Specificity was 85% for ultrasound, 94% for CT and palpation, and 87% for PET. PET produced false negative results in 13.4% of all cases. Inflammation was detected in these cases. The positive predictive value was marginally better for PET than for ultrasound (77% vs. 75%). It proved to be lower than the values for palpation (86%) and CT (88%). Negative predictive value was 90-91% for all imaging procedures. CONCLUSION: In the primary diagnosis of nodal alterations in the head and neck region, a PET scan has the same diagnostic value as ultrasound or CT. By imaging the metabolism of a suspected nodal metastasis, PET can help to improve the assessment of regions with uncertain anatomic features. To avoid false positive results, acute and chronic inflammatory alterations have to be ruled out before the PET imaging.

Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits.

BACKGROUND: In the ongoing discussion concerning the realization of an epiretinal prosthesis for electric stimulation of retinal ganglion cells, long-term fixation of such a device is a crucial question. We evaluated surgical techniques for implantation and fixation of electrically inactive microelectrode arrays (MA) into the retinas of rabbits and secondary tissue reactions to the implant. METHODS: Vitrectomy and laser coagulation of the prospective fixation area were performed in rabbits. Implantation of MAs was performed 3 weeks later in 10 animals. The MA was fixated using retinal tacks. The follow-up included ophthalmoscopy and electrophysiology. At the end of the follow-up, the enucleated eyes were processed for light microscopy using standard procedures and grinding techniques. RESULTS: Nine of 10 rabbits were implanted without serious complications. Clinical and electrophysiologic data through 6 months of follow-up did not indicate any adverse effect of the surgery, the implant, or the tack itself. No change in retinal architecture underneath the implant was found by light microscopy. In these cases, the implant was stable at its original fixation area. In three cases, mild cataract formation was observed, and in one case, a total retinal detachment was found. CONCLUSION: Tack fixation of electrode arrays for electric stimulation of the inner retinal surface seems to be a useful approach in long-term implantation of an epiretinal prosthesis.