Volume 28, No. 6/2009(Nov/Dec)
|
 Clinical Neuropathology
Die Online-Versionen der Zeitschriften werden jeweils vor Erscheinen der Print-Ausgabe aktualisiert. Alle Inhalte dieser Website stehen Abonnenten der Zeitschrift nach einmaliger Registrierung ohne Mehrkosten zur Verfügung. Um die Artikel im PDF-Format betrachten zu können, benötigen Sie die Adobe Reader® Software.
|
| Preis für gesamte Ausgabe: 50.00$ |
 |
Editorial
Clinical Neuropathology – Euro-CNS journal since 2006
J. Weis und J. Hainfellner
Abstract
J. Weis und J. Hainfellner
Myology
Mild clinical and histopathological features in patients who carry the frequent and causative malignant hyperthermia RyR1 mutation p.Thr2206Met
H. Rueffert, M. Wehner, V. Ogunlade, CD. Meinecke and R. Schober
Abstract
H. Rueffert1, M. Wehner1, V. Ogunlade2, CD. Meinecke1 and R. Schober2
1Department of Anesthesiology and Intensive Care Medicine, University Hospital of Leipzig and 2Institute of Neuropathology, University of Leipzig, Leipzig, Germany
Objective: Malignant hyperthermia (MH) is a classically unapparent pharmacogenetic disorder of the skeletal muscles triggered by inhalational anesthetics or depolarizing muscle relaxants. The disposition to MH is inherited in an autosomal-dominant manner and is primarily due to mutations in the gene for the ryanodine receptor type 1 (RyR1). The present study intended to analyze whether mild muscular symptoms (elevation of the resting CK, cramps in the calves, slight calf hypertrophy) may be associated with susceptibility to MH and/or with histopathological changes. Methods: A muscle biopsy was taken from 12 out of 44 blood relatives (three generations) of a large family and was investigated with the halothane/caffeine in vitro contracture test (IVCT). Afterwards a histological, histochemical and immunhistological examination was performed. Altogether in 29 persons the DNA was analyzed for mutations in the RyR1-gene. Results: Eight persons were diagnosed as susceptible to MH (MHS) by the IVCT, 4 were MH negative. All MHS persons carried the MH causative c.6617C > T (Thr2206Met) mutation and showed slight clinical signs of a myopathy as well as mild biopsy changes with isolated hypotrophic fibers and disseminated small areas with reduction of oxidative staining (multi-minicore like lesions). The Thr2206Met mutation was identified in another further 9 relatives who also experienced mild myopathological features. Clinical MH incidents were not reported in this large family. Conclusion: The RyR1 Thr2206Met mutation is one of the most frequent mutations in the European MH population but carriers are normally healthy. In this study we could demonstrate that the MH causative Thr2206Met mutation may also be associated both with clinical symptoms of a mild myopathy and histopathological changes in the oxidative inter myofibrillar network.Correspondence to:
Dr. H. Rueffert
University Hospital of Leipzig
Department of Anesthesiology and Intensive Care Medicine
Liebigstr. 20, 04103 Leipzig, Germany
Email: henrik.rueffert@medizin.uni-leipzig.de
Infectious Diseases
Disseminated Fusarium infection with brain abscesses in a lung transplant recipient
B.K. Kleinschmidt-DeMasters
Abstract
B.K. Kleinschmidt-DeMasters
Departments of Pathology, Neurology, and Neurosurgery, University of Colorado Health Sciences Center, Aurora, CO, USA
Objective: To detail a case of disseminated Fusarium infection in an immunocompromised adult. Fusarium sp. infections are an important cause of fungal keratitis in immunocompetent patients and a recent outbreak related to use of a specific type of contact lens solution made national and international newspaper headlines. While reports of disseminated infection in immunosuppressed patients have appeared over the last 30 years, few have emphasized the neuropathological aspects of this emerging pathogen. Patient and methods: Woman with pulmonary sarcoidosis necessitating bilateral lung transplants 4 months prior to her demise who was soon readmitted with viral pneumonia. She developed targetoid skin lesions of her face and thigh; she succumbed before biopsy could be performed. Results: Autopsy revealed systemic organ infection involving lungs, gastrointestinal tract mucosa, bilateral kidneys, and skin. Foci of acute cerebritis showed vessels occluded by hyphal, septate fungi. Fungal culture remains the gold standard for diagnosis, and culture grew Fusarium. Conclusion: Fusarium is resistant to standard antifungal therapies; the increasing use of antifungal medications – as either treatment or prophylaxis – may shift more infections toward unusual species such as Fusarium.Correspondence to:
B.K. Kleinschmidt-DeMasters, MD
University of Colorado Health Sciences Center
Department of Pathology, F768
12605 E. 16th Avenue
Aurora, CO 80045, USA
Email: bk.demasters@ucdenver.edu
Infectious Diseases
Japanese encephalitis – serial CT findings and neuropathology in an autopsy case
Z. Kobayashi, K. Tsuchiya, O. Yokota, C. Haga, T. Arai, H. Akiyama, M. Kotera and H. Mizusawa
Abstract
Z. Kobayashi1,2, K. Tsuchiya2,3, O. Yokota2,4, C. Haga2, T. Arai2, H. Akiyama2, M. Kotera5 and H. Mizusawa1
1Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, 2Tokyo Institute of Psychiatry, 3Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, 4Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, and 5Department of Neurology, Tsuchiura Kyodo Hospital, Tsuchiura Ibaraki, Japan
The patient was a 17-year-old man, who developed Japanese encephalitis in the autumn of 1990 in Japan. He was admitted to our hospital 4 days after onset because of consciousness disturbance. On admission, neurological examination demonstrated left hemiparesis, neck stiffness, and Kernig’s sign. He developed generalized tonico-clonic seizure, and required a respirator on the next day of admission. Brain CT 10 days after onset demonstrated hypodensities in the right hippocampus, and the CT obtained 39 days after onset showed whole brain atrophy and hypodensities in the anterior portion of the bilateral thalamus. He died 40 days after onset. Postmortem examination demonstrated perivascular and parenchymal infiltration of lymphocytes and macrophages, proliferation of microglia and astrocytes, and necrosis in the gray matter of the brain. Involvement of the hippocampus and thalamus on CT seemed to reflect the severe lesions characterized by cellular infiltration and necrosis. We discussed for the first time the correlation of CT and neuropathological findings in a patient with Japanese encephalitis.Correspondence to:
Z. Kobayashi, MD
Tokyo Institute of Psychiatry
2-1-8 Kamikitazawa, Setagaya-ku
Tokyo, Japan, 156-8585
Email: zen@bg7.so-net.ne.jp
Tumor
No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson’s syndrome and Cushing’s disease in vitro and in vivo
J. Kreutzer, I. Jeske, B. Hofmann, I. Blumcke, R. Fahlbusch, M. Buchfelder and R. Buslei
Abstract
J. Kreutzer1, I. Jeske2, B. Hofmann1, I. Blumcke2, R. Fahlbusch1, M. Buchfelder1 and R. Buslei2
1Department of Neurosurgery and 2Institute of Neuropathology, University Hospital Erlangen, Germany
Objective: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing’s disease (CD) and Nelson’s syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. Materials and methods: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 – 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 µM rosiglitazone repeatedly over a time period of 14 days. Results: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls. Conclusion: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.Correspondence to:
J. Kreutzer, MD
Department of Neurosurgery
Klinikum rechts der Isar
Technische Universität München
Ismaninger Straße 22
81675 Munich, Germany
Email: juergen.kreutzer@lrz.tum.de
Tumor
Intracranial cholesteatoma – case report and critical review
T.E. Habesoglu, N. Balak, M. Habesoglu, E. Zemheri, N. Isik, I. Elmaci and E. Egeli
Abstract
T.E. Habesoglu1, N. Balak2, M. Habesoglu1, E. Zemheri3, N. Isik2, I. Elmaci2 and E. Egeli1
1Department of Otorhinolaryngology, Haydarpasa Numune Education and Research Hospital, 2Department of Neurosurgery, 3Department of Pathology, Göztepe Education and Research Hospital, Istanbul, Turkey
Objective: Chronic otitis media is a potentially serious disease because of its complications, most of which are common in conjunction with cholesteatomas. There is variance in the terminology used by neurosurgeons, otorhinolaryngologists and neuropathologists. Synonyms for cholesteatoma found in the literature include epidermoid tumor, epidermoid cysts and epithelial inclusion cyst. Intracranial extension of an acquired cholesteatoma is a rarely documented occurrence. Patients/Material and Methods: A 47-year-old woman who had undergone a right tympanomastoidectomy 20 years previously, presented with a long history of mild headaches that had become progressively more severe over the last 3 years. Clinical and radiological evaluation of the patient raised the suspicion of an intracranial cholesteatoma. Results: A right temporal craniotomy was performed. The mass was completely excised and histopathological study revealed the tumor to be a cholesteatoma. The patient’s post-operative recovery was uneventful. Conclusions: Cholesteatomas possess the capacity for eroding bone and can have an insidious onset, but once established, grows relentlessly and destroys neighboring structures. Since a gradual intracranial involvement does not usually cause acute symptoms of increased intracranial pressure, the correct diagnosis may be difficult. Detailed clinical and radiographic studies in particular are diagnostically helpful. Because of the high incidence of delayed recurrence, life-long follow-up is required. The inconsistency in the histopathological classification of intracranial cholesteatomas should be clarified.Correspondence to:
N. Balak, MD
Department of Neurosurgery
Göztepe Education and Research Hospital
Istanbul, 34730, Turkey
Email: drnacibalak@yahoo.com
Tumor
5-lipoxygenase pathway promotes cell proliferation in human glioma cell lines
K. Ishii, M. Zaitsu, N. Yonemitsu, Y. Kan, Y. Hamasaki and M. Matsuo
Abstract
K. Ishii1,2, M. Zaitsu1, N. Yonemitsu3, Y. Kan1,2, Y. Hamasaki1 and M. Matsuo1
1Department of Pediatrics, Faculty of Medicine, Saga University, Saga, 2Department of Pediatrics, Saga Handicapped Children’s Hospital, Saga, and 3Department of Pathology, Sasebo Central Hospital, Nagasaki, Japan
Objective: 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes (LTs), that might promote carcinogenesis. We investigated 5-LO expression and examined whether the 5-LO pathway is associated with the proliferation of human brain tumors. Methods: We immunohistochemically evaluated the profile of 5-LO expression in various types of brain tumors obtained from 42 patients, and examined the proliferative effects of the 5-LO pathway in human glioma cell lines using a proliferation assay. Results: Immunohistochemistry of glioblastomas, astrocytomas, meningiomas, medulloblastomas, craniopharyngiomas, ependymomas, neurinomas, oligodendrogliomas, malignant lymphomas, dysembryoplastic neuroepithelial and metastatic brain tumors revealed 5-LO expression in the cytoplasm and nuclei or nuclear envelopes of tumor cells. The 5-LO inhibitor A861 and the LTA4 hydrolase inhibitor Bestatin dose-dependently suppressed the proliferation of A172 cells, a glioma cell line. Conclusions: We confirmed the expression of 5-LO in various human brain tumors and demonstrated the partial suppression of tumor growth by inhibitors of the 5-LO-LTA4 hydrolase pathway in human glioma cell lines. The 5-LO-LTA4 pathway might play roles in the proliferation of human glioma cells.Correspondence to:
M. Zaitsu, MD
Department of Pediatrics
Faculty of Medicine
Saga University
5-1-1 Nabeshima
Saga City 849-8501, Saga, Japan
Email: zaitsum@cc.saga-u.ac.jp
Tumor
Benign meningioma developing late lung metastases: case report and review of the literature
T. Psaras, G. Pantazis, V. Steger, R. Meyermann, J. Honegger and R. Beschorner
Abstract
T. Psaras1, G. Pantazis2, V. Steger3, R. Meyermann2, J. Honegger1 and R. Beschorner2
1Department of Neurosurgery, 2Institute for Brain Research, Eberhard-Karls-University Tübingen, 3Department of Thoracic Surgery, Schillerhöhe-Hospital, Gerlingen, Germany
Here we report the case of a 65-year-old female with a histologically benign parietal falcine meningioma who developed multiple lung metastases 15 years after tumor resection. The meningioma was initially incompletely resected due to invasion of the sagittal sinus. Since it was diagnosed as a benign meningothelial meningioma Grade I WHO, the residual tumor was followed with serial imaging without adjuvant treatment. The patient subsequently developed lung lesions later identified as metastases. The lung lesions were successfully removed surgically and histologically diagnosed as meningothelial meningioma Grade I WHO. A repeat brain MRI revealed the known residual meningioma with no signs of interval tumor growth, but did demonstrate occlusion of the sagittal sinus. In the further course, the residual meningioma was completely removed. A review of the literature revealed only 15 well-documented cases of benign meningiomas that metastasized in an interval of up to 12 years after primary tumor resection. This case illustrates that histologically benign meningiomas Grade I WHO with stable disease of the primary tumor have the potential to develop hematogenous metastases even after a long time interval.Correspondence to:
PD Dr. R. Beschorner
Institute for Brain Research
University of Tübingen
Calwerstraße 3
72076 Tübingen, Germany
Email: rudi.beschorner@med.uni-tuebingen.de
Tumor
Malignant transformation of an intraaxial-supratentorial neurenteric cyst – Case report and review of the literature
C.P. Dunham, B. Curry and M. Hamilton
Abstract
C.P. Dunham1, B. Curry2 and M. Hamilton3
1Children’s and Women’s Health Center of British Columbia, University of British Columbia, Vancouver, British Columbia, 2Department of Pathology and Laboratory Medicine/Calgary Laboratory Services, and 3Department of Clinical Neurosciences, Foothills Medical Center, University of Calgary, Calgary, Alberta, Canada
Neurenteric cysts are “rare benign mass forming developmental abnormalities” that usually affect young adults. Neurenteric cysts are thought to be derived from primitive endoderm, and form as a result of faulty endodermal-notochordal separation at 3 weeks of embryogenesis. Neurenteric cysts are lined by simple-to-pseudostratified respiratory/gastrointestinal-like epithelium; as such, these lesions closely resemble colloid and Rathke’s cleft cysts. Anatomically, neurenteric cysts most frequently arise in an intradural-extraaxial location anterior to the cervical-thoracic spinal cord. Intracranial neurenteric cysts are uncommon but have a tendency to reside in the infratentorial compartment. Malignant transformation of the epithelial component of neurenteric cysts is decidedly rare. Of the 3 reported cases of neurenteric cysts with malignant transformation, all were intracranial (2 infratentorial and 1 supratentorial) and extraaxial. We describe a 58-year-old female with a supratentorial-intraaxial lesion that is consistent with a neurenteric cyst exhibiting malignant transformation into an invasive mucinous papillary cystadenocarcinoma. Areas of direct transition between typical benign neurenteric cyst epithelia and malignant epithelia (i.e., carcinoma in situ), highlighted by an abrupt change in the Ki-67 proliferative index, were identified, and supported the primary nature of this brain neoplasm. Metastatic workup at the time of presentation was unremarkable, and immediately up until being lost to follow-up 38 months after gross total resection, routine follow-up MR imaging had not detected a recurrence. To our knowledge, this would be the first reported case of malignant transformation within a supratentorial-intraaxial neurenteric cyst.Correspondence to:
C.P. Dunham, MD, FRCPC
Clinical Assistant Professor
University of British Columbia
Children’s and Women’s Health
Center of British Columbia
L218 Shaughnessy Building
4500 Oak Street,
Vancouver, BC, V6H 3N1, Canada
Email: cdunham@cw.bc.ca
Euro-CNS News
Society News of the European Confederation of Neuropathological Societies
