Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

[Rapid frozen sections in neuropathology]. / Der Schnellschnitt in der Neuropathologie.

Neuropathological evaluation of frozen sections requires a) special expertise in neuropathological specimen assessment and neurooncology as well as b) a trustful and open communication culture with the neurosurgeons. In addition to frozen sections, cytological examinations of smear and touch preparations as supporting methods are available to reach a correct diagnosis: these additional methods should therefore be performed whenever possible. Besides evaluation of biopsy specimens, appraisal of resection specimens and resection margin controls are of high clinical relevance. In the case of diffusely infiltrating central nervous system (CNS) neoplasms, in particular gliomas, resection margin control is often not feasible in contrast to other types of solid tumor.

5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institutuion.

OBJECTIVE: Among the factors determining prognosis in patients with malignant glioma, the extent of resection has long been controversial. However, recent data have shown that patients derive a survival benefit from extensive tumour resection. 5-aminolaevulinic acid (5-ALA)-induced fluorescence renders more complete resection possible in malignant glioma. We report on the feasibility of the method in daily clinical practice, the benefits for patients and surgeons, the technical limitations and the methods we have devised of overcoming these limitations. METHODS: We describe our initial experience in 74 cases undergoing gross total resection, partial resection and biopsy. Fluorescence intensity and histological data are analysed, specificity and sensitivity are calculated according to fluorescence intensity, and the pitfalls and limitations are defined. The fluorescence signal was quantified via digital video data and by single photon count. RESULTS: Solid fluorescence signals define tumours with a sensitivity of 0.98 and a specificity of 1.0. Vague fluorescence reduces sensitivity to 0.76 and specificity to 0.85. Limitations of 5-ALAassisted surgery are apparent within the inter-observer interpretation of solid or vague fluorescence, heterogeneity of gliomas, invasion beyond the resection cavity and intercell heterogeneity of porphyrin IX fluorescence. CONCLUSION: 5-ALA-induced PIX fluorescence improves the results in high-grade glioma surgery for gross total resection. Specificity and sensitivity in regions of solid fluorescence are very high. Quantitative analysis of fluorescence intensity corrects the reduced reliability of the method in areas of vague fluorescence and renders gross total resection more feasible without additional risk to the patient. PIX fluorescence is easy to implement in daily neurosurgical practice and side effects are very few. Heterogeneous tumours with lower grade elements and satellite lesions cannot be reliably resected using fluorescence-assisted surgery alone. In these cases the additional use of intra-operatively updated imaging-based neuronavigational methods (MR, ultrasound) is needed.

[Bilateral deafness, an initial manifestation of meningeal carcinomatosis]. / Surdité bilatérale, manifestation initiale d'une carcinomatose méningée.

Three cases of bilateral deafness with cytologically-demonstrated meningeal carcinomatosis are reported. The first patient, a 64-year old man, presented with bilateral deafness, gait disturbances, and bilateral facial paresis. The second patient, a 78-year-old man, had bilateral deafness, unsteady gait and fluctuations in consciousness. The last patient, a 69-year-old man, complained of bilateral deafness and severe headache, and presented with right facial paresis and left laterodeviation while walking. All three patients had abnormal cochleo-vestibular findings and brainstem auditory evoked responses (BAER) that suggested peripheral lesions with absent or very delayed I waves. The brain CT scans with an without contrast enhancement were entirely normal, and the diagnosis was established by lumbar puncture. From our own cases and a review of the literature, deafness in meningeal carcinomatosis may start unilaterally but becomes bilateral in less than a week. Vestibular disturbances may not be apparent, but they can be demonstrated in almost all cases. Facial paresis or plegia is also a very frequent finding. The destruction of the eighth and seventh cranial nerves is probably due to direct infiltration by neoplastic cells as well as to ischemia through compression of the nerve supplying vessels. The 3 cases presented here emphasize once again the important fact that meningeal carcinomatosis remains a cytological diagnosis, several lumbar punctures being sometimes necessary, and that cerebrospinal fluid studies cannot yet be supplanted by other diagnostic techniques like contrast-enhanced CT or MRI with gadolinium.

Multicentric tumor manifestations of high grade gliomas: independent proliferation or hallmark of extensive disease?

OBJECTIVE: Improvements in microneurosurgical techniques, radiotherapy and chemotherapy for the treatment of high grade gliomas resulted in better local tumor control and longer progression-free survival. Multicentric (MC) lesions located distant from the initial resection area contribute to treatment failure in a growing number of patients. These MC lesions may develop within the course of the disease (metachronous) or may already be present at the time of first tumor manifestation (synchronous). To look for mechanisms and regular patterns behind MC glioma manifestations and to investigate whether they are "a second primary tumor" or the result of continuous diffuse glioblastoma cell invasion, we retrospectively analyzed the initial and all follow-up MR studies of our high grade glioma (HGG) patients. PATIENTS AND METHODS: MR studies of 247 consecutive patients treated for HGG at a single institution were analyzed. MC tumor manifestation was defined as more than one gadolinium enhancing lesion within the brain on MRI without a connecting signal alteration in T2 sequences and/or without a connecting hypointense mass in T1 sequences. The minimal distance to define two solitary lesions was set at >10 mm. According to these specifications 40 patients showed MC tumor manifestations in their MR studies on admission or during treatment of their disease. The MR studies of these cases were retrospectively analyzed for patterns in MC tumor manifestation and progression. Topographical specifications and delay in manifestation were used to explain possible pathways of development. Kaplan Meyer survival graphs for metachronous and synchronous MC disease were calculated. RESULTS: 24 patients showed MC tumor manifestation at the time of admission. 16 cases developed MC manifestation within a follow-up period of 3-57 months. The location of all lesions could be categorized into one of three distinct patterns (white matter, subependymal, intraventricular). The patterns showed individual and location-specific time gaps to metachronous manifestation. Calculated from the time of first tumor diagnosis, the median survival was longer for patients with metachronous MC lesions (353 days, p<0.05) compared to patients with synchronous MC lesions (110 days) or patients without multicentricity (234 days). Patients with metachronous lesions showed a similar survival (72 days) as patients with synchronous MC lesions (110 days) once they developed MC disease. CONCLUSION: The topographical patterns and temporal characteristics of MC disease suggest that all manifestations share common mechanisms such as an active migratory process. Our data therefore do not support the concept of an independent MC development of multiple gliomas.

Heralding manifestations of basilar artery occlusion with lethal or severe stroke.

BACKGROUND: Basilar artery occlusion usually causes severe disability or death. Until the recent developments in local intra-arterial or systemic intravenous fibrinolysis, interest in early diagnosis was low because there was no satisfactory treatment. Thus there is little information about the initial phase of the disease. OBJECTIVE: To report on the early clinical features and patterns of evolution of severe symptomatic basilar artery occlusion. METHODS: 24 patients with established basilar artery occlusion (confirmed by angiography or at necropsy) were reviewed retrospectively, focusing on the early clinical aspects and time course of the disease. RESULTS: The most common initial symptoms were motor deficits (16/24, including facial palsies), articulatory speech difficulties (15/24), vertigo, nausea or vomiting (13/24), and headaches (10/24). The most frequent objective initial findings were motor deficits (22/24), facial palsies (19/24), eye movement abnormalities (15/24), lower cranial nerve deficits (15/24), altered level of consciousness (12/24), and bilateral extensor plantar responses (9/24). Onset of the disease was gradual in nearly all patients and in half the warning signs were present for up to two months before the final stage. Headaches and visual disturbances were early signs, while speech difficulties and motor deficits were late signs. Once permanent neurological deficits were present, the final illness was reached within six hours in 41%, between six and 24 hours in 32%, and in two to three days in 27%. CONCLUSIONS: All the patients reviewed presented some symptoms and signs pointing to brain stem involvement. Only 8% (2/24) had an acute course with no adequate warning signs.

Morphology of dentate granule cells in the human epileptogenic hippocampus.

Hippocampal dentate granule cells in temporal lobe epilepsy (TLE) patients with mesial sclerosis (MTLE) are reported to be hyperexcitable compared to those in patients with a mass lesion outside the hippocampus (MaTLE) (Williamson, Clin Neurosci 1994;2: 47-52). To determine if such hyperexcitability is associated with an altered morphology of these neurons, Lucifer Yellow-filled granule cells from MTLE patients were compared with those from MaTLE. The morphology of granule cells in both subject groups resembles closely that of human granule cells described previously by Golgi studies. About 40% of human granule cells have basal dendrites. Additionally their apical dendrites are much more limited in their spread in the longitudinal axis of the hippocampus contributing perhaps to a much more narrow lamellar organization than in rats. Analysis of variance computed on 21 morphometric parameters reveals a significant increase in the length of the portion of the dendrite in the inner molecular layer (IML), and a decrease in length in the outer third of the molecular layer in MTLE, compared to MaTLE. Factor analysis performed on the morphometric features of each group of neurons reveals that in the MaTLE neurons the most distinctive feature is the total dendritic length and the overall distribution of spines on them, whereas in MTLE a lengthening and elaboration of the dendrites in the IML is most distinctive. Previous observations of increased synaptic terminals containing neuropeptides, and neurotransmitter receptors in the IML taken in conjunction with an elaboration of granule cell dendrites in this region, suggest considerable synaptic reorganization within the IML of the MTLE hippocampus which may contribute to its epileptogenicity.

Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus.

The AMPA-type glutamate receptor subunits GluR1 and GluR2/3 were localized by immunohistochemistry with subunit-specific antibodies in hippocampi removed surgically from patients with temporal lobe epilepsy for the control of seizures. The flip and flop splice variants of the subunits were localized by in situ hybridization histochemistry with specific oligoprobes. In patient hippocampi that were not the seizure focus, the GluR1 subunit proteins were diffusely expressed on the dendrites of neurons in all regions. In contrast, in these same hippocampi, the GluR2/3 subunit proteins were expressed strongly on the soma and proximal dendrites of principal neurons in all regions. The flip variant of these subunits was localized in the hilus and fields of Ammon's Horn (CA), while the flop variants were prominent on the dentate granule cells. In the epileptogenic hippocampus, while immunoreactivity was decreased in all fields that showed neuronal loss, there was an increased expression of GluR1 on the dendritic excrescences on the proximal dendrites of hilar neurons and CA3 pyramidal neurons, as well as expression of GluR2/3 in hilar neuron excrescences. Electron microscopic examination confirmed that the GluR1 immunoreactivity was only in dendritic processes, particularly dense at the postsynaptic membranes. Such expression of GluR1 may provide for an enhanced glutamatergic response by these neurons. GluR2/3 was also significantly increased on the dendrites of dentate granule cells in the epileptogenic hippocampus and may provide some protection against excitotoxic injury by reducing calcium flux into neurons.