Comparative experimental study of argon plasma and bipolar coagulation techniques.

BACKGROUND: Argon plasma coagulation (APC) is based on the principle of ionised argon creating conductive plasma between an activating electrode and tissue surface and is used as an effective alternative coagulation technique in various surgical disciplines. This trial aims to compare thermal injury in rat brain caused by APC and conventional bipolar coagulation technique. METHODS: A controlled study design with constant power setting and application time was established. Twenty rats were randomised into the APC and bipolar groups. Each group of ten rats had 20 treated lesions. Early and late histopathological changes, as well as maximum extent of the lesion after 48 hours (h) and 12 days were studied in overall 20 lesions. FINDINGS: Although the maximum depth of the lesions was different in APC (2.2 mm) and bipolar (1.8 mm) groups after 48 h, this did not achieve statistical significance (p=0.151). The superficially coagulated area was significantly larger after APC compared with the bipolar technique at the 48 h time point (p=0.032). After twelve days there were no differences in penetration depth (p=0.310) or coagulated area (p=0.222). CONCLUSION: Tissue defects after APC application on rat brains were comparable to conventional bipolar technique in this trial. The results suggest that argon plasma coagulation (APC) is an effective coagulation technique.

Two novel cell specific receptor proteins, CRLR and CD 117 in human glial tumors.

OBJECTIVE: CRLR (calcitonin receptor-like receptor) and CD 117, the gene product of c-kit have been shown to be expressed in cells of glial tumors, especially in those with higher malignancy. Here we report the distribution of these peptides in various cellular compartments within those tumors. MATERIAL: Both receptor proteins have been investigated in 95 glial tumor biopsies of different grades. METHODS: Both proteins were visualized by immunohistochemistry with antibodies either commercially available or raised for this purpose. RESULTS: Both receptor peptides can be identified in or around tumor blood vessels. CRLR occurs in some endothelial cells, especially in the microvascular proliferations of glioblastoma multiforme, whereas CD 117 preferentially occurs in cells of the thickened vascular wall within cells of pericyte or fibroblast morphology. Both antigens are found in addition in few neoplastic cells of overt astrocyte morphology. CONCLUSIONS: The occurrence of identical antigens in glial tumor blood vessels and in neighboring tumor cells underlines the common origin of "mesenchymal" and "neuroepithelial" components of such (malignant) glial neoplasms.

Ganglioside (GD2) expression and intermediary filaments in astrocytic tumors.

The search of proliferation markers in astrocytic tumors that may serve as targets for therapeutic interventions, is in full progress. Membrane-bound signal transducers for growth factors are amongst the substances of interest. Gangliosides are lipid-sugar compounds localized on the cell membrane that are thought to modify pertinent signals and, therefore, may influence a variety of functions in normal and pathologic conditions including those that act upon tumor growth. Intracranial supratentorial astrocytic gliomas of the adult represent a tumor group, that may be divided into three grades of malignancy, the most anaplastic member being the glioblastoma. A stepwise anaplasia is assumed and accompanied by genetic events that are partly specific for these grades. In earlier investigations, it had been shown that there is a tendency towards formation of more simple members of the ganglioside family with ongoing malignancy of those tumors. Yet, the results were only partly congruent and the correlation to tumor grades rather loose. We, therefore, investigated the occurrence of triaose gangliosides within these tumors in situ by immunohistochemistry. In this paper, we corroborate our earlier observation that triaose gangliosides preferentially occur within the cytoplasm of large protoplasmic and gemistocytic astrocytes. The potency of the expression of GD2 is calculated and plotted against the expression of two markers of intermediate glial filaments, namely GFAP (glial fibrillary acid protein) and vimentine. A high interdependence of the three compounds could be demonstrated by correlation analysis. Thus, the conclusion must be drawn that the correlation of ganglioside patterns to the proliferation of astrocytic tumors is as poor as that of GFAP or vimentin expression, respectively.

Argon plasma coagulation (APC) in brain tumor surgery: experimental study and clinical experiences.

OBJECTIVE: The present study aims to provide preliminary results of the thermal effects on rat brain tissue after argon plasma coagulation (APC). It also presents and discusses the clinical experiences in the treatment of brain tumor using APC. MATERIALS AND METHODS: A controlled study of APC in the rat brain was conducted. Twelve rats were randomly divided into 2 experimental groups. In the first group (n = 6), histopathological evaluation was performed 2 days following the coagulation. In the second group (n = 6), the evaluation was performed 12 days post operation. In a prospective study of APC-treated tumor tissue in 3 patients, the depth of plasma penetration and histological alteration were evaluated. RESULTS: In the animal experiment, extent of tissue defect became significantly smaller after 12 days (p = 0.010). The maximum depth of tissue alteration after APC application was limited to 2.15 mm (range: 1.5-2.15 mm) at day 2. The histological alteration of tissue after the thermal injury can be divided into 3 zones. In addition, the depth of tissue alteration in the APC-treated human brain tumor was measured in vertical and horizontal planes under light microscope. Similar to the animal experiment result, penetration of the plasma energy in human brain tumors was limited to a maximum of 2.13 mm (range: 1.6-2.13 mm). CONCLUSION: The limited depth of energy penetration may confirm APC as a safe and beneficial tool for coagulation of human brain tissue. However, further clinical studies are required to evaluate the suitability and indications of this method in brain tumor treatment.

Primary and transplanted ENU induced rat tumors in neurooncology.

In neurooncology transplanting, tumors can be used for many purposes e.g. to solve questions concerning the etiology and pathogenesis of such tumors or their management. Experimentally induced and transplanted tumors of the nervous system become reproducible in their morphology and growth parameters after about 12 subsequent intracerebral passages. During the period from the first to the 12th intracerebral generations, a simplification of the histology and a reduction of the induction times take place. Nowadays the growth behavior of such tumors can be followed by imaging methods such as MRI if specially adapted to small animals. Our results are based on the investigation of over 2350 experimentally induced tumors of the central and peripheral nervous system that were diagnosed according to the rules of human and rodent brain tumor classification and various subgroups of this sample, analyzed by electron microscopy, postmortal angiography and MRI.

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

BACKGROUND: Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. AIM: To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. METHODS: Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. RESULTS: All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. CONCLUSIONS: This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

[Pigmented form of orthochromatic leukodystrophy]. / Die pigmentierte Form der orthochromatischen Leukodystrophie.

The pigmentary type of orthochromatic leukodystrophy (van Bogaert-Nyssen disease) is a hardly known neurological disorder usually with late onset that is very difficult to diagnose in vivo. Neuropathologically, the disorder features noninflammatory demyelination and the presence of pigmented macrophages and astrocytes that may contain iron. Clinically, van Bogaert-Nyssen disease can lead to death within a few years and is characterized by dementia, psychiatric abnormalities, epileptic seizures, spastic pareses, and occasionally extrapyramidal motor symptoms. This report presents a typical case and an overview of the literature. Furthermore, galactocerebroside could be documented in remaining macrophages and astrocytes by immunohistochemistry. This possibly indicates a dysfunction in sphingolipid breakdown and could relate the pigmented form of orthochromatic leukodystrophy to the genetically defined globoid cell leukodystrophy (Krabbe's disease). Thus, the rather heterogeneous pool of orthochromatic leukodystrophies could be further narrowed.

Rupture of an internal carotid artery aneurysm during angiography with leakage of contrast medium via an external ventricular drain.

With a ruptured intracranial aneurysm producing subarachnoid haemorrhage (SAH) cerebral angiography is currently used for identification of the affected vessel. Aneurysm rerupturing is one of the more serious complications of cerebral angiography and has been frequently described. We report a 61-year-old man who presented with SAH who had rerupture of a large aneurysm of the internal carotid artery during angiography. A substantial amount of contrast medium escaped via a ventricular drain. The three main risk factors for rerupture of an aneurysm are: angiography performed within 6 h of the primary SAH, an aneurysm on the internal carotid artery and an unfavourable Glasgow coma score.

Is there a final common pathway in mitochondrial encephalomyopathies? Considerations based on an autopsy case of Kearns-Sayre syndrome.

A case of Kearns-Sayre syndrome (KSS) diagnosed 18 years prior to death due to stroke and heart failure with postnatal onset was followed over 15 years and confirmed by postmortem examination. Within the brain, an old cystic infarction of the left hemisphere was found. Other features included white matter gliosis and cerebellar atrophy. Equal or similar features were observed in other conditions thought to be due to failure of mitochondrial metabolism, therefore, a common evolution of neuropathological changes must be discussed.

Intraspinal pannus formation at C6 in a patient with rheumatoid arthritis causing severe cervical cord compression. A case report.

We report a rare case of cervical cord compression caused by intraspinal pannus formation at C6 in a patient with long-term rheumatoid arthritis. No atlantoaxial abnormalities were seen. The imaging findings are presented and the pathology discussed.

Helium (argon) plasma coagulation in neurosurgery. morphology of tissue damage and reparation.

Plasma coagulation, used in some neurosurgical operative settings, is currently under experimental investigation for the precise assessment of the kind and extent of tissue damage. We established a standardised trial to investigate the effects of helium (argon) plasma coagulation - H(A)PC - on rat brain tissue. The tissue reactions were observed with common methods of morphology including immunohistology and electron microscopy. A time dependent profile of the tissue reactions was performed from day 1 after operation up to 6 weeks. The tissue reaction consisted of clearly demarcated concentric zones. The depth of the lesion was about 1 mm maximally, at the beginning. Reparative forces acted at variance both in the different layers and at the edges versus the center of the damage. A manifold but reproducible picture emerges in the various compartments allowing the study of different aspects of organisation and/or elimination of tissue components. This study has demonstrated that a defined circumscribed and reproducible small lesion can be performed with H(A)PC. As in other areas of surgery, this technique has proven to be minimally traumatic. Clinical application of this technique in neurosurgery is therefore promising. In addition, H(A)PC lesions are obviously best suited for morphological studies of early and late reparative reactions in cells and tissues.

[Klaus Joachim Zülch: Partner to neurosurgery, advocate of neurology and the neuropathological basis]. / Klaus Joachim Zülch: Neurochirurgie, Neurologie und die neuropathologischen Grundlagen.

Klaus Joachim Zülch (1910-1988) since 1959 head of a department of the german Max-Planck-Society, deeply influenced the neurological sciences in post-war Germany. The department with the name Abteilung für allgemeine Neurologie (i.e. department of general neurology) constituted a section of the renowned Max-Planck-Institut für Hirnforschung (i.e. institute for brain research) and found its place in Cologne. At the same time he was in charge of the local neurology unit of the municipal Cologne hospital, on the right Rhine riverside in Köln (Cologne) Merheim. In this double position he was able to focus his work as a neurologist on the major issues of this specialty, that at this time were not in the center of neurological interest: The connection of basic science i.e. morphology with important themes such as raised intracranial pressure, brain swelling and edema, brain and spinal chord circulation disturbances, head injuries and - in the first line - tumors of the central nervous system. This broad approach to essential issues in the field was probably due to his upbringing in german neurological tradition. His first contact with this specialty took place in Otfrid Foersters neurological clinic in Breslau, today in Poland, before World War II. Otfrid Foerster, a neurological encyclopedist, exerted a deep influence upon Klaus Joachim Zülch lifelong. Here he also came in contact with Percieval Bailey with whom he shared the obsession to classify brain tumors since then. This preoccupation became fruitful when he started collaboration with Wilhelm Tönnis 1936 at the time still in Würzburg. The collaboration continued, when Tönnis moved to Berlin, during and after World War II up to 1959, when Klaus Joachim Zülch became head of the mentioned department of the german Max-Planck-society. At this time, important contributions already existed concerning brain injuries, brain edema and tumor classification. The couple Wilhelm Tönnis and Klaus Joachim Zülch may well be compared to the team formed by Harvey Cushing and Percieval Bailey. Their respective philosophies were equally identical, namely to classify tumors of the central nervous system through a pragmatic approach that would facilitate the communication between neuropathologist, neurosurgeon, neurologist and of course be ultimately as helpful as possible to the patient. Since 1959 Zülchs research turned to the topics of brain hypoxia, circulatory disturbances and stroke, notwithstanding that his interest remained with the other items, whenever new or old questions came up. The occupation with tumors became even once more intense when the WHO installed a reference center for brain tumor classification at his place in Cologne. In the new field of brain circulation, Klaus Joachim Zülch tried once again to bring basic science and clinical practise together and to draw the neurologists attention upon these frequent and important conditions, a development that gained increasing importance under the heading of "stroke unit" in our days. Klaus Joachim Zülch therefore may be regarded as neurologist ahead of his time trying to cover the epidemiologically important and frequent themes and establishing equal partnership with neurosurgery The connection with the scientific basis, i.e. morphology in different variations at the time under a common roof was crucial in his understanding of the work as neurologist.

[Decompressive craniectomy for severe intracranial hypertension due to cerebral infarction or meningoencephalitis]. / Kraniektomie bei Hirndrucksteigerung durch Hirninfarkte und Meningoenzephalitis.

We describe the clinical course and outcome following decompressive craniectomy in six patients. Five patients suffered from severe intracranial hypertension due to middle cerebral artery infarction. In one patient the cause was bacterial meningoencephalitis. Acute clinical and neuroradiological signs of intracranial hypertension were seen in all cases. Following ineffective conventional brain edema therapy, decompressive craniectomy was undertaken. In five cases intracranial pressure was sufficiently lowered. One patient developed transtentorial herniation with subsequent brain death. Four patients with middle artery infarction showed moderate neurological disorders and one patient with bacterial meningoencephalitis recovered completely after treatment. Craniectomy in malignant middle artery infarction should be taken into consideration if conventional brain edema therapy does not sufficiently reduce critically raised intracranial pressure. Craniectomy provides development of brain herniation. This treatment may reduce high lethality rate and high frequency of severe neurological disorders.

Endothelial proliferation, neoangiogenesis, and potential de novo generation of cerebrovascular malformations.

OBJECT: To date, both arteriovenous malformations (AVMs) and cavernomas have been considered to be congenital malformations. A recent survey of the literature has shown the potential for de novo generation of both familial and sporadic cavernomas as well as AVMs. Therefore, it was of interest to determine the biological behavior of these lesions in detail. METHODS: The proliferative and angiogenic capacities of the endothelium of 13 cavernomas and 25 AVMs obtained in patients recently treated (1997-1998) at one institution were studied. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), MIB-1, and vascular endothelial growth factor (VEGF) and its receptor Flk-1 was performed using standard staining procedures. Positive immunostaining of the nuclei of endothelial cells was observed in specimens of both AVMs and cavernomas for PCNA (80% of AVMs and 85% of cavernomas), and Flk-1 (80% of AVMs and 31% of cavernomas). Endothelial expression of VEGF in the 18 incompletely embolized AVMs was found in 72% of cases but only in 28% of the seven cases in which patients did not undergo endovascular treatment: it was found in 38% of cavernomas. Endothelial expression of MIB-1 was found in 12% of AVMs but in no cavernomas. CONCLUSIONS: These results indicate that there is endothelial proliferation as well as neoangiogenesis in cerebral cavernomas and AVMs. The increased level of angiogenesis in only partially obliterated AVMs underscores the need for radical and complete occlusion of cerebral AVMs to avoid recurrences and further risks of morbidity.

Early and late morphological effects of experimental HPNS--animal model of psychosis?

The high pressure neurological syndrome (HPNS), a neurological condition during elevated pressure especially in deep diving, has been simulated with experimental animals. Rats were subjected to 61 bars with slow pressure increase and one or two hours constant high pressure; subsequently the pressure was released to sea level within 20 seconds--leading to immediate oxygen depletion and death of animals--or with slow decompression rates allowing survival. In all animals, brains and partly other organs were investigated morphologically. In animals sacrificed immediately, subtle changes in different brain regions were found: symmetrical occurrence of dark neurons in the hippocampus formation, cortex and brain stem, reduced expression of tyrosin hydroxylase in the substantia nigra and enhanced expression of Bax protein in some of these regions. The dark neurons were only observed after aldehyde fixation, otherwise the brains were unaltered despite ultrarapid decrease of highly elevated pressure. In animals that were allowed to survive for different time periods, some of these subtle changes were equally noted by light and electron microscopy. Furthermore, the ventricles were enlarged, the astrocytic reaction in the hippocampus increased and some signs of the destruction of the adrenal gland were visible. We conclude, that HPNS leads to minimal changes within the nervous system. The behaviour of animals during pressure was slightly altered, the weights after the experiments reduced, but no lasting sequelae were noted. Since both in human and experimental deep diving conditions signs of psychosis were reported, this HPNS model must be considered as a tentative animal model of human psychosis.

Treatment-induced neoangiogenesis in cerebral arteriovenous malformations.

We investigated the angiogenetic and proliferative activity of the endothelium of 30 consecutive surgical cases of AVM treated at our institution by immunohistochemical detection of the PCNA, MIB-1, Flk-1 and VEGF antibodies. Endothelial positive immunostaining was observed in 87% of the cases for PCNA, in 20% for MIB-1, and in 80% for Flk-1. Of 22 individuals treated with incomplete embolization prior to surgery, 17 showed an expression of VEGF (77%), but only two of the eight patients (25%) who were treated without prior embolization exhibited such an immunoreaction (P=0.0086). The proliferation and growth of cerebral AVMs is documented by endothelial expression of PCNA and MIB-1. The statistically significantly higher expression of VEGF in partially obliterated (embolized) AVMs is most likely caused by transient regional hypoxia within the AVM nidus that mediates neoangiogensis. It points out the clinical relevance of a complete occlusion in order to avoid neovascularization associated with subsequent morbidity and mortality.

[Fulminant course of falciparum malaria]. / Foudroyanter Verlauf einer Malaria tropica.

HISTORY AND ADMISSION FINDINGS: A 57-year-old white man had been travelling in Kenya for vacation until 14 days before admission. Due to apprehension about side effects, the patient had refused any malaria prophylaxis. Ten days before admission he developed low grade temperatures and suffered from pain in the limbs, from nausea and vomiting. A new episode of tachyarrhythmia was diagnosed two days before admission and was treated by his general practitioner. Finally he was admitted to our hospital because of high temperatures, chills and progressive clinical deterioration. Autopsy revealed prominent congestion of liver, spleen and cerebral vessels as well as subdural and subarachnoidal hemorrhage. INVESTIGATIONS: In both thin and thick peripheral blood smears Plasmodium parasites were demonstrated in approximately 30% of the eryhthrocytes and the diagnosis of Plasmodium falciparum was immediately confirmed by an immunological test. TREATMENT AND COURSE: Due to the fulminant clinical and neurological deterioration with progressive hypoxaemia, the patient required ventilator therapy already one hour after admission. Therapy with chinine and doxycycline was initiated and exchange transfusion was considered. However, due to hyperkalaemia and cardiac arrest, the patient died 4 hours after admission due to parasitic hemolysis. CONCLUSIONS: Severe Plasmodium falciparum infection in non-immunized patients is a medical emergency and requires immediate diagnosis and treatment. Malaria should always be considered in the differential diagnosis in persons who have travelled to endemic areas and presenting not only with temperatures, but also with non-specific clinical signs, like cardiac arrhythmias. Although never entirely effective, chemoprophylaxis is highly recommended.

Morphology of tissue damage caused by permanent occlusion of middle cerebral artery in mice.

In two series of experimental occlusion of the middle cerebral artery (MCA) in mice, the time course and the evolution of morphological changes were followed. Both series comprised control animals used in experiments for the screening of neuroprotective and therapeutic effects after focal ischemia. In both series the left MCA was permanently occluded and the animals were sacrificed by perfusion fixation at certain time intervals following occlusion. In the first series the follow up was continued until the 30th day after ischemia. In the second, the observation period was extended to two months. The general question was addressed, whether or not such experimental settings can contribute to the understanding of cellular (necrosis vs apoptosis) and tissue (resorption vs scar) reaction. In the two series the technical procedures were only slightly different. Nevertheless, the development of morphological sequelae was at variance. Differences in tissue reaction in both sets revealed features that were rarely observed in previous protocols. In the first series, infarct areas were different in size, often a central part near the meninges was preserved and gave rise to a prominent mesenchymal reaction. In the second series, infarcts had almost constant size and mesenchymal reaction changes were minimal. The end product in both series, however, was a shallow groove much smaller than the primary well-demarcated defect. We conclude that minor technical variations of MCA occlusion in the mouse demonstrate the variability of occlusion sequelae due to collateral irrigation known from human cerebral pathology. On the cellular level, neuronal death is obviously completed during the first 24 hours in the infarct core. Thus, the mechanism of neuronal damage can only be best observed by morphology at the transition between completed territorial necrosis and unchanged tissue: shrunken neuronal perikarya develop into pycnotic nuclei, that may be interpreted as apoptosis. A second area of partial damage is marked by gliosis. Astrocytic reaction extended far beyond the infarct border, even to the contralateral hemisphere and could represent a component of size compensation.