Susanne A. Kuhn

Methylation-specific multiplex ligation-dependent probe amplification in meningiomas.

Genomic loss and promotor methylation contribute to inactivation of tumor suppressor genes (TSGs). Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a relatively new method for simultaneous detection of both these alterations. Here, we apply MS-MLPA to a series of 15 meningiomas of different WHO grades. The two MS-MLPA probe sets used detect copy number changes in 55 unselected TSGs and promotor methylation in a subset of 36 of these genes. Our findings concerning genomic deletions are concordant with previously published studies using alternative techniques. The number of aberrations identified per tumor increased with histopathologically determined grading. The most frequent single event was deletion of the von Hippel-Lindau (VHL) gene in 12 of the 15 tumors. Moreover, VHL deletion status was associated with presence/absence of peritumoral edema. Methylation was rare, being observed in only four tumors and in each case restricted to a single gene. We conclude that a meningioma-specific MS-MLPA probe set would be a valuable tool for both research and diagnostic approaches in these tumors.

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.

Cerebral metastasis of a primary heart sarcoma

Primary cardiac sarcomas are exceptionally rare tumours. A brain metastasis of a primary cardiac sarcoma has never been reported before. Although we know lots of primary malignomas spreading to the brain, we never observed cerebral metastases of an atrial spindle cell sarcoma. Cardiac sarcomas are more likely to haematogenously metastasize to the lung or the liver. Here, we describe the case of a young man, who suffered from a cerebral metastasis of a spindle cell sarcoma in the left heart atrium nine years ago. Postoperative whole brain irradiation with 30 Gy was performed. Later on, the patient experienced a local recurrence within the left atrium accompanied by cardiac arrhythmia and mitral valve insufficiency. This case is the very first description of a true cerebral metastasis from a primary heart sarcoma. Therefore, clear treatment paradigms are not established. Further case illustrations and the publication of larger patient series are mandatory, whenever possible.

„Spinal cord stimulation“ in Höhe des Conus medullaris

Injuries of the pudendal nerve, due to a perineal tear during delivery for example, can cause significant and debilitating neurological deficits. Aconuresis and anal incontinence, as well as sensory loss of the outer genitals or even impotency in men are the well known consequences. In addition some patients suffer from a severe neuropathic pain syndrome which is resistant to conservative treatment options. Epidural spinal cord stimulation at the level of the terminal cone of the spinal cord may be a new and successful therapeutic concept in otherwise untreatable cases.

[Spinal cord stimulation at the level of the conus medullaris : treatment option for therapy-resistant postoperative neuralgia of the pudendal nerve].

Injuries of the pudendal nerve, due to a perineal tear during delivery for example, can cause significant and debilitating neurological deficits. Aconuresis and anal incontinence, as well as sensory loss of the outer genitals or even impotency in men are the well known consequences. In addition some patients suffer from a severe neuropathic pain syndrome which is resistant to conservative treatment options. Epidural spinal cord stimulation at the level of the terminal cone of the spinal cord may be a new and successful therapeutic concept in otherwise untreatable cases.

„Spinal cord stimulation“ in Höhe des Conus medullaris@@@Spinal cord stimulation at the level of the conus medullaris: Behandlungsoption bei therapierefraktärer postoperativer Neuralgie des N. pudendus@@@Treatment option for therapy-resistant postoperative neuralgia of the pudendal nerve

Injuries of the pudendal nerve, due to a perineal tear during delivery for example, can cause significant and debilitating neurological deficits. Aconuresis and anal incontinence, as well as sensory loss of the outer genitals or even impotency in men are the well known consequences. In addition some patients suffer from a severe neuropathic pain syndrome which is resistant to conservative treatment options. Epidural spinal cord stimulation at the level of the terminal cone of the spinal cord may be a new and successful therapeutic concept in otherwise untreatable cases.