Bernhard R. Fischer

Cerebral AL λ-amyloidoma: Clinical and pathomorphological characteristics. Review of the literature and of a patient

Background. Amyloid deposits within the brain can be found in a heterogeneous group of diseases. Some of them involve only the central nervous system (AD); others are of systemic origin. Isolated deposits either in the brain, cranial nerves or within the spinal neural structures are extremely rare. So far, we do not know the natural origin, nor the clinical course. Methods. We reviewed the overall published cases as far as available and added our own case to learn more about the natural history, clinical and imaging characteristics of this rare brain lesion. Results. Together with our own case, 27 patients with cerebral amyloidoma were collected in the literature. The lesion always occurred supratentorially, moreover in another two cases also infratentorially. The initial symptoms as well as the results of different neuroimaging features were not specific. There was no predominance for sex and localization. Diagnosis could only be established by histopathological examination after surgical intervention. No recurrence was seen after radical resection; but there was progression in some cases of tumor biopsy. Conclusion. Complete surgical removal of cerebral AL amyloidoma seems to be the only way to prevent progression or recurrence of such a brain lesion.

Coexistence of cerebral aneurysm and meningioma—Pure accident?

OBJECTIVESnCoexisting intracerebral aneurysms and meningiomas occur relatively rarely, without a clear relationship, although an aneurysm can be located within a meningioma. The aim of this retrospective study was to identify possible explanations for the coexistence of these conditions and to present a rationale for treatment strategies.nnnPATIENTS AND METHODSnNinety-five patients with coexistent meningioma and aneurysm were found in the National Library of Medicine, and 11 more patients were retrieved from our own database.nnnRESULTSnCo-occurrence of both pathologies, sometimes solitary, sometimes multiple, was mostly found in women (3:1). Clinical symptoms in the majority of patients were caused by tumour growth, whereas aneurysm rupture was seen only in a few cases. Consequently tumour resection was performed first in 58 out of the 95 patients, and aneurysm treatment in 38 patients. From available data, the mortality rate three decades before was approximately 40%, but decreased in the last years, due to microsurgical and endovascular techniques. All of our patients were alive after 1 year of follow-up. In patients with intratumoural aneurysms, only three published and one our own case, were treated for both pathologies.nnnCONCLUSIONSnThe coexistence of meningioma and aneurysm seems to be a coincidence. Treatment should primary focus on the cause of presenting symptoms, but in cases with intratumoural aneurysm, the aneurysm should be treated first. Due to the development of microsurgical and endovascular techniques peri-procedural mortality and morbidity has decreased.

Endovascular management of tandem extracranial internal carotid artery aneurysms with a covered stent.

Purpose: To illustrate the endovascular technique for treating tandem arterial aneurysms in the distal carotid artery. Case Report: A 49-year-old woman presented with progressive swelling of the neck caused by a pulsatile tumor. Angiography demonstrated 2 aneurysms of the extracranial internal carotid artery near the skull base, so surgery was not a therapeutic option. Both aneurysms were successfully excluded with deployment of a single Wallgraft across both lesions; no complications were encountered. At 2-year follow-up, the patient is doing well, without any sign of aneurysm reperfusion. Conclusions: The presented case demonstrates that stenting of tandem aneurysms may be performed even in the carotid artery. Nevertheless, this treatment should be considered as a therapeutic option only in selected cases.

Dynamic ICG fluorescence provides better intraoperative understanding of arteriovenous fistulae.

BACKGROUND: Sufficient perfusion is crucial during and after vascular neurosurgical procedures. Intraoperative indocyanine green (ICG) angiography has evolved into a useful tool in aneurysm and arteriovenous malformation surgery. Semiquantitative ICG fluorescence analysis Flow 800 may, in addition, lead to a better understanding of local perfusion. OBJECTIVE: We report the applicability and utility of semiquantitative ICG fluorescence in the surgical treatment of 5 patients with pial or dural arteriovenous fistulae. METHODS: Five patients with pial or dural arteriovenous fistulae were operated on using intraoperative semiquantitative ICG fluorescence Flow 800 (5 mg ICG bolus via central venous line). Before and after occlusion of fistulae, rise time of parenchyma and transit time from artery to parenchyma were measured. RESULTS: The analysis of flow parameters allowed detection of small fistulae and revealed a significant change in flow dynamics in the draining vein after surgical occlusion. ICG “flow” analysis showed rise time and transit time to be significantly shorter comparing pre-occlusion with post-occlusion (P = .025 and P = .039, respectively), leading to a significantly enhanced perfusion of neighboring brain parenchyma. CONCLUSION: In all 5 patients, dynamic analysis of fluorescence revealed a better understanding of intravascular rheology intraoperatively, allowing confident identification and treatment of pathology. Dynamic ICG fluorescence measurements provide additional perfusion information about flow characteristics in the draining vein and tissue perfusion, which facilitates surgical treatment of arteriovenous fistulae. ABBREVIATIONS: AVF, arteriovenous fistula AVM, arteriovenous malformation ICG, indocyanine green ROI, region of interest

Rationale of Hyperbaric Oxygenation in Cerebral Vascular Insult

Cerebrovascular diseases and especially ischemic stroke are a leading cause of death. They occur mostly due to an insufficient oxygen (O2) supply to the central neural tissue as a result of thromboembolic events and/or obstructive vessel disease. The primary damage of the brain tissue cannot be restored. However, adequate therapy could minimize secondary impairment of brain tissue and restore neuronal function in the so-called penumbra region. Apart from reopening occluded vessels, additional O2 supply is essential for survival of malfunctioning neural tissue. Breathing of 100% O2 under hyperbaric conditions, hyperbaric oxygenation (HBO), is the only method to increase the O2 concentration in tissue with impaired blood supply. Experimental as well as clinical studies have reported a positive effect of HBO therapy. Survival rate has increased under HBO therapy and neurological outcome has improved. The optimal levels of pressure as well as duration and numbers of HBO sessions need to be specified to avoid undesirable effects. Unfortunately, many questions remain unanswered before routinely recommending HBO as additional therapy in clinical practice. In this review we consider the (patho-)physiological background of HBO-therapy, the latest results of experimental and clinical studies and stress the evidence in patients with cerebrovascular disease.

MGMT promoter methylation status in anaplastic meningiomas

Anaplastic meningioma [World Health Organization (WHO) grade III] is characterized by aggressive biological behavior and recurrent tumor growth [1]. Radiation therapy is commonly employed after both total and subtotal resection, but effective chemotherapeutic regimens are lacking [2]. Hypermethylation of the O-methylguanine-DNA methyltransferase (MGMT) promoter is an important prognostic marker and also predicts response to therapy with alkylating agents (e.g., temozolomide) in patients with malignant gliomas [3]. While in benign meningiomas (WHO grade I) MGMT promoter methylation is rare or absent [4, 5] and temozolomide lacked efficiency in a small series of grade I meningiomas refractory to treatment [6], in anaplastic meningiomas, i.e., those neoplasms most likely to be considered for adjuvant treatment, MGMT methylation status has only been assessed in one and three cases, respectively [4, 5] and the role of temozolomide remains unclear. We thus aimed to examine MGMT methylation status in a large series of anaplastic meningiomas. Formalin-fixed paraffin-embedded tissue samples from all anaplastic meningiomas diagnosed from 1989 to 2009 were retrieved from the archives of the Institute of Neuropathology, Münster. In addition, available samples of formerly grade II or recurrent grade III tumors of these patients were also retrieved. All samples were reviewed neuropathologically according to WHO criteria [1]. After isolation and bisulfite conversion (EZ DNA Methylation-Gold Kit; Zymo Research, Orange, CA), DNA from representative tumor material was subjected to methylation-specific polymerase chain reaction (PCR) as described previously [7]. Controls included clones representing methylated and unmethylated bisulfite converted DNA [8] as well as enzymatically methylated human genomic DNA (Zymo Research). Using the above approach, a total of 55 samples from 30 patients could be examined. The median age of the 17 females and 13 males was 66 years (range 33–92 years). Eighty-five percent of the tumors were of supratentorial location. As shown in Fig. 1, MGMT promoter methylation status was negative in all cases except for a single specimen. This 57-year-old male suffered from recurrent grade III meningioma, showing hypermethylation of the MGMT promoter region on repeated analyses. Using the same methodology, MGMT promoter methylation status was positive in 90 out of 194 malignant astrocytic tumors (46%, data not shown). B. Brokinkel S. Peetz-Dienhart W. Paulus M. Hasselblatt (&) Institute of Neuropathology, University Hospital Münster, Domagkstraße 19, 48149 Münster, Germany e-mail: hasselblatt@uni-muenster.de

Aquaporin-4 in glioma and metastatic tissues harboring 5-aminolevulinic acid-induced porphyrin fluorescence

INTRODUCTIONnAquaporin channels (AQPs) are a group of integral membrane proteins that regulate the transport of water through cell membranes. Previous studies have shown that up-regulation of AQP1 and AQP4, two of the predominant AQPs in the human brain, in high grade glial tumors contribute to cerebral edema. Others link AQPs to the regulation of human glioma cell migration and invasion. The aim of this study was to determine AQPs expression in tumor tissue harboring 5-aminolevulinic acid (ALA)-induced porphyrin fluorescence with flow cytometry and compare it to the expression in normal brain tissue.nnnMETHODSnTissue samples were obtained from fluorescing brain tumors of 26 patients treated with ALA prior to surgery (20 mg/kg b.w.). Expression levels of aquaporin channels were measured in primary tissue cultures using a FACS CANTO I flow cytometer. A control group consisted of four non-fluorescing tissue samples, the C6 and the U87 cell line.nnnRESULTSnNineteen gliomas (14 high grade, 5 low grade) and 7 metastases were analyzed. On the 4th post-operative day, expression levels of AQP4 channels, but not of AQP1 channels, were significantly increased in samples from fluorescing tissue compared to non-fluorescing tissue. In addition we could see how ALA induces fluorescence in metastases.nnnCONCLUSIONnFlow cytometry appears to be an auspicious method for the analysis of porphyrins and AQPs in primary brain cell tumor cultures. ALA fluorescing tissue showed higher AQP4 expression compared to normal brain tissue. The demonstrated expression in a context with ALA could open a targeted therapeutic spectrum, for example to selectively target AQP4.

Intracerebral mass lesion diagnosed as cryptococcoma in a patient with sarcoidosis, a rare opportunistic manifestation induced by immunosuppression with corticosteroids

Cryptococcal infection of the central nervous system (CNS) typically affects patients with HIV infection. In addition, opportunistic infections can also occur during immunosuppressive therapies. Some patients develop cryptococcal meningitis. Cryptococcomas, however, are rarely observed. A 42-year-old patient with sarcoidosis known for 2½xa0years presented with a cerebral mass lesion primarily thought to be CNS sarcoidosis. Stereotactic biopsy and extensive micro- and macrobiological investigations revealed a cryptococcoma which had emerged from cryptococcal meningitis despite 3 months of treatment. Differential diagnosis of cerebral cryptococcoma is difficult due to the unspecific findings in the CSF analysis if C. neoformans fails to be detected using Indian ink staining or PCR studies. In this case, stereotactic biopsy and pathohistological examination revealed C. neoformans causing intracerebral mass lesion. Intensive treatment with antifungal drugs was followed by remission of all symptoms. In conclusion, cryptococcoma of the CNS represents a very important indication of mass lesions in patients suffering from sarcoidosis and treated with corticosteroids.

Hyperbaric oxygen in neurosurgery

BackgroundThe therapeutic use of pure oxygen, even under hyperbaric conditions, has been well established for about 50xa0years, whereas the discovery of oxygen occurred 250xa0years earlier. Many neurosurgical patients suffer from brain tissue damage, due to reduced blood flow, obstructive vessel disease, or as a result of traumatic brain injury.Methods and resultsThe application of pure oxygen in these patients is the only method of increasing the O2 concentration in tissue with impaired blood supply and can minimize secondary impairment of brain tissue.DiscussionIn this brief historical overview we focus on the development and evidence of hyperbaric oxygenation in this specific field of insufficient oxygen supply to the central neural tissue.ConclusionWith the use of modern biological methods and new study designs, HBO has a place in evidence-based treatment of patients with neural tissue damage.

Inflammatory thromboembolic complication after craniopharyngioma surgery

SummaryAside from endocrine or visual disturbances an appearance of other complications after craniopharyngioma surgery is rare. We report a case of delayed brain infarction in the postoperative period of craniopharyngioma resection. A 30-year-old man presented with visual impairment and diabetes insipidus. Imaging revealed a partly cystic, partly contrast enhancing intra-/suprasellar mass lesion. The patient underwent craniotomy with resection of the tumour. Histological examination revealed an adamantinomatous craniopharyngioma. Early postoperative an aseptic meningitis, which was diagnosed clinically as well as by laboratory and CSF analysis, resolved spontaneously. One week later a cerebral incident with infarction in the peripheral territory of MCA on the left side occurred. For this unusual event with a review of the literature a thromboembolic origin is suggested on the basis of inflammatory vascular involvement after an attack of aseptic meningitis.