Michael Brodhun

Overexpression of protease-activated receptor type 1 (PAR-1) in glioblastoma multiforme WHO IV cells and blood vessels revealed by NCAM-assisted glioblastoma border labeling

Abstract Glioblastomas are neuroepithelial tumors with lost cellular differentiation and tenfold increased growth rates compared to low-grade gliomas. Despite of very aggressive treatment options based on surgery, irradiation, and chemotherapy, the prognosis of affected patients has remained poor and showed only slight improvements during the last 30 years. Research on glioblastoma border zone was hindered by the tumor’s intense invasion into the brain parenchyma and the lack of suitable tumor cell markers. Nevertheless, the compact tumor mass and tumor invasion zone are composed of distinct cell types that need to be distinguished from each other to be addressed selectively. As the isoform 140 of the neural cell adhesion molecule (NCAM-140) was recently demonstrated to be lost in human gliomas with rising WHO grade, human multiform glioblastomas were characterized as a NCAM-140 negative entity displaying three main distinct invasion patterns. Evaluation of putative therapy targets within the tumor tissue and tumor invasion zone has been made possible through NCAM-140 negativity. In the present study, brain tissue controls and human glioblastoma samples with compact tumor mass and invasion areas were analyzed for their vascularization at the tumor border and the expression of thrombin receptor protease-activated receptor type 1 (PAR-1) within tumor tissue and vascular vessel walls. Use of NCAM-140 enabled the identification of the tumor invasion zone and its experimental investigation. Tissue vascularization was found to be significantly increased in the compact tumor mass of glioblastomas compared to their invasion zone and tumor-free controls with a significantly high and specific overexpression of PAR-1 within tumor cells and within tumor blood vessels depending upon the tumor area. This suggests thereby a functional role of the thrombin receptor PAR-1 in glioma cell malignancy and glioblastoma neoangiogenesis.

Doppelbilder und kardiogener Schock

ZusammenfassungDie idiopathische Riesenzellmyokarditis ist eine seltene und häufig tödlich verlaufende entzündliche Herzerkrankung, die zu kongestivem Herzversagen oder ventrikulären Arrhythmien führt und gehäuft kombiniert mit anderen immunvermittelten Erkrankungen auftritt. Wir berichten den Fall einer 39-jährigen Patientin, die sich mit intermittierenden Doppelbildern und Bulbusmotilitätsschmerz, dem typischen klinischen Bild einer okulären Myositis, vorstellte und kurz darauf eine rasch progrediente Linksherzinsuffizienz aufgrund einer Riesenzellmyokarditis entwickelte, an deren Komplikationen sie letztlich verstarb. Autoptisch wurden die okuläre Myositis und die Riesenzellmyokarditis gesichert. Der Fallbericht unterstreicht die Bedeutung frühzeitiger und engmaschiger echo- und elektrokardiographischer Verlaufsuntersuchungen bei dem klinischen Verdacht auf eine okuläre Myositis, um durch frühzeitiges Erkennen einer kardialen Beteiligung rechtzeitig eine Herztransplantation als einzige bisher wirksame Therapieoption anstreben zu können.SummaryIdiopathic giant cell myocarditis is a rare and frequently fatal inflammatory heart disease which leads to congestive heart failure or ventricular arrhythmias. It is often associated with other autoimmune disorders. We report a 39-year-old woman who first presented with diplopia and painful eye movements, the typical clinical picture of orbital myositis. Shortly afterwards, she developed rapidly progressive congestive heart failure due to giant cell myocarditis, which took a fatal course within some weeks. Autopsy confirmed both disorders. This case report underlines the importance of early and repeated monitoring of cardiac function, if orbital myositis is suspected, in order to consider cardiac transplantation, the only efficacious treatment of giant cell myocarditis, in time.

Diplopia and cardiogenic shock

ZusammenfassungDie idiopathische Riesenzellmyokarditis ist eine seltene und häufig tödlich verlaufende entzündliche Herzerkrankung, die zu kongestivem Herzversagen oder ventrikulären Arrhythmien führt und gehäuft kombiniert mit anderen immunvermittelten Erkrankungen auftritt. Wir berichten den Fall einer 39-jährigen Patientin, die sich mit intermittierenden Doppelbildern und Bulbusmotilitätsschmerz, dem typischen klinischen Bild einer okulären Myositis, vorstellte und kurz darauf eine rasch progrediente Linksherzinsuffizienz aufgrund einer Riesenzellmyokarditis entwickelte, an deren Komplikationen sie letztlich verstarb. Autoptisch wurden die okuläre Myositis und die Riesenzellmyokarditis gesichert. Der Fallbericht unterstreicht die Bedeutung frühzeitiger und engmaschiger echo- und elektrokardiographischer Verlaufsuntersuchungen bei dem klinischen Verdacht auf eine okuläre Myositis, um durch frühzeitiges Erkennen einer kardialen Beteiligung rechtzeitig eine Herztransplantation als einzige bisher wirksame Therapieoption anstreben zu können.SummaryIdiopathic giant cell myocarditis is a rare and frequently fatal inflammatory heart disease which leads to congestive heart failure or ventricular arrhythmias. It is often associated with other autoimmune disorders. We report a 39-year-old woman who first presented with diplopia and painful eye movements, the typical clinical picture of orbital myositis. Shortly afterwards, she developed rapidly progressive congestive heart failure due to giant cell myocarditis, which took a fatal course within some weeks. Autopsy confirmed both disorders. This case report underlines the importance of early and repeated monitoring of cardiac function, if orbital myositis is suspected, in order to consider cardiac transplantation, the only efficacious treatment of giant cell myocarditis, in time.

Differential diagnosis of solitary neurosarcoidosis

Sarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5-9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.ZusammenfassungDie Sarkoidose ist eine durch nicht verkäsende Granulome charakterisierte Multisystemerkrankung, die sich in über 90% der Fälle an der Lunge manifestiert. Nach klinischen Kriterien wird eine Beteiligung des Nervensystems bei 5–9% der Erkrankten beschrieben, autoptisch sogar in bis zu 25% der Fälle. Ein isolierter Befall des Nervensystems stellt eine Rarität und zugleich ein diagnostisches Problem dar, da trotz vielfältiger neurologischer Ausfälle erst der histologische Nachweis nicht verkäsender epitheloidzelliger Granulome die Diagnose sichert. Anhand des Falles einer 51-jährigen Patientin mit chronischer basaler Meningitis und Affektion des peripheren und zentralen Nervensystems bei isolierter Neurosarkoidose wird die Diagnostik und Differenzialdiagnostik der Erkrankung diskutiert.SummarySarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5–9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.

Differenzialdiagnose der isolierten Neurosarkoidose@@@Differential diagnosis of solitary neurosarcoidosis

Sarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5-9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.ZusammenfassungDie Sarkoidose ist eine durch nicht verkäsende Granulome charakterisierte Multisystemerkrankung, die sich in über 90% der Fälle an der Lunge manifestiert. Nach klinischen Kriterien wird eine Beteiligung des Nervensystems bei 5–9% der Erkrankten beschrieben, autoptisch sogar in bis zu 25% der Fälle. Ein isolierter Befall des Nervensystems stellt eine Rarität und zugleich ein diagnostisches Problem dar, da trotz vielfältiger neurologischer Ausfälle erst der histologische Nachweis nicht verkäsender epitheloidzelliger Granulome die Diagnose sichert. Anhand des Falles einer 51-jährigen Patientin mit chronischer basaler Meningitis und Affektion des peripheren und zentralen Nervensystems bei isolierter Neurosarkoidose wird die Diagnostik und Differenzialdiagnostik der Erkrankung diskutiert.SummarySarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5–9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.

Differenzialdiagnose der isolierten Neurosarkoidose

Sarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5-9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.ZusammenfassungDie Sarkoidose ist eine durch nicht verkäsende Granulome charakterisierte Multisystemerkrankung, die sich in über 90% der Fälle an der Lunge manifestiert. Nach klinischen Kriterien wird eine Beteiligung des Nervensystems bei 5–9% der Erkrankten beschrieben, autoptisch sogar in bis zu 25% der Fälle. Ein isolierter Befall des Nervensystems stellt eine Rarität und zugleich ein diagnostisches Problem dar, da trotz vielfältiger neurologischer Ausfälle erst der histologische Nachweis nicht verkäsender epitheloidzelliger Granulome die Diagnose sichert. Anhand des Falles einer 51-jährigen Patientin mit chronischer basaler Meningitis und Affektion des peripheren und zentralen Nervensystems bei isolierter Neurosarkoidose wird die Diagnostik und Differenzialdiagnostik der Erkrankung diskutiert.SummarySarcoidosis is an inflammatory multisystemic disease characterised by noncaseating epithelioid granulomas. The lung is affected in over 90% of patients. According to clinical criteria, the nervous system is involved in 5–9%. However, in autopsy series this number increases to 25%. Solitary involvement of the nervous system without signs of systemic disease is rare and diagnostically cryptic. Due to the wide variety of neurologic symptoms, definite diagnosis of sarcoidosis is possible only by histopathological proof of noncaseating epithelioid granulomas. We report a 51-year-old woman who presented with chronic basal meningitis and involvement of the peripheral and central nervous system due to solitary neurosarcoidosis. Diagnostic procedures and differential diagnosis are discussed.