Predictors and impact of early cerebral infarction after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cerebral infarction is a frequent and serious complication of aneurysmal subarachnoid hemorrhage (SAH). This study aimed to identify independent predictors of the timing of cerebral infarction and clarify its impact on disease course and patients' outcome. METHODS: All consecutive patients with SAH admitted to our institution from January 2005 to December 2012 were analyzed. Serial computed tomography (CT) scans were evaluated for cerebral infarctions. Demographic, clinical, laboratory and radiological data of patients during hospitalization as well as clinical follow-ups 6 months after SAH were recorded. RESULTS: Of the 632 analyzed patients, 320 (51%) developed cerebral infarction on CT scans. 136 patients (21.5%) with early cerebral infarction (occurring within 3 days after SAH) had a significantly higher risk of unfavorable outcome than patients with late infarction [odds ratio (OR) 2.94; P = 0.008], a higher in-hospital mortality (OR 3.14; P = 0.0002) and poorer clinical outcome after 6 months (OR 0.54; P < 0.0001). The rates of decompressive craniectomy (OR 1.96, P = 0.0265), tracheostomy (OR 1.87, P = 0.0446), the duration of intensive care unit stay and mechanical ventilation were significantly higher in patients with early infarction. In multivariate analysis, Hunt and Hess grades 4 and 5 (OR 2.06, P = 0.008), Fisher grades 3 and 4 (OR 3.99, P = 0.014), sustained elevations of intracranial pressure >20 mmHg (OR 5.95, P < 0.0001) and early vasospasm on diagnostic angiograms (OR 3.01, P = 0.008) were predictors of early cerebral infarction. CONCLUSION: Early cerebral infarction after SAH is associated with severe clinical course and unfavorable outcome and can be reliably predicted by poor initial clinical condition, thick subarachnoid clot, early angiographic vasospasm and sustained elevations of intracranial pressure.

Partial agonism at the human alpha(2A)-autoreceptor: role of binding duration.

Temperature-induced changes of affinity and efficacy of the alpha2-adrenoceptor full agonist UK14,304 and the partial agonists clonidine and guanfacine were investigated to elucidate the mechanism of partial agonism at the terminal alpha2-autoreceptor. The effect of temperature on the efficacy of the substances was tested in 3H-noradrenaline release experiments at 37 degrees C and at room temperature. Human neocortical slices were prelabeled with 3H-noradrenaline, superfused, and stimulated electrically under autoinhibition-free conditions. Furthermore, saturation binding experiments with human neocortical synaptosomes were performed at 37 degrees C and 17 degrees C to evaluate the influence of temperature on the affinity of 3H-clonidine and 3H-UK14,304. Temperature-induced changes of the association and dissociation rate constants of 3H-UK14,304 and 3H-clonidine were assessed in corresponding kinetic binding experiments. Our experiments reveal that clonidine and guanfacine lose efficacy when the temperature is lowered, whereas no change was noted for the full agonist UK14,304. Moreover, the affinity of clonidine and guanfacine was shown to decrease at lower temperature. Kinetic experiments indicated that the loss of affinity observed for 3H-clonidine at 17 degrees C is due to a marked reduction of the association rate. The loss of efficacy of the partial agonists is most likely related to the short binding duration; partial agonists do not bind long enough to the receptor to mediate a maximum response. The discrepancy between the time required to elicit a maximum response and the actual binding time may be greater for partial agonists at lower temperatures, thus, causing the intrinsic activity to decline.

[Von Hippel-Lindau disease. Interdisciplinary patient care]. / Von-Hippel-Lindau-Erkrankung. Interdisziplinäre Patientenversorgung.

Von Hippel-Lindau disease is an important hereditary tumor syndrome with a clear option for effective treatment if diagnosed in time. Interdisciplinary cooperation is the key to successful management. Major components of the disease are retinal capillary hemangioblastomas, hemangioblastomas of cerebellum, brain stem and spine, renal clear cell carcinomas, pheochromocytomas, multiple pancreatic cysts and islet cell carcinomas, tumors of the endolymphatic sac of the inner ear, and cystadenomas of the epididymis and broad ligament. A well structured screening program should be performed at yearly intervals.

Neuronal electrical high frequency stimulation enhances GABA outflow from human neocortical slices.

Electrical high frequency stimulation of the globus pallidus internus or the subthalamic nucleus has beneficial motor effects in advanced Parkinson's disease. The mechanisms underlying these clinical results remain, however, unclear. From previous studies it is proposed that the gamma-aminobutyric acid (GABA) system is involved in the effectiveness of electrical high frequency stimulation. In these experiments, human neocortical slices were stimulated electrically (130 Hz) in vitro, and GABA outflow was measured after o-phthaldialdehyde sulphite derivatization using HPLC with electrochemical detection. Our results could demonstrate that high frequency stimulation (HFS) significantly increased basal GABA outflow in the presence of submaximal concentrations of the voltage-gated sodium channel opener veratridine. This effect could be abolished by the GABA antagonists bicuculline or picrotoxin. These results suggest that HFS has an activating effect on GABAergic neuronal terminals in human neocortical slices, depending on sodium and chloride influx. Since GABA plays a role in CNS disorders of basal ganglia, anxiety and epilepsy, its neocortical modulation by HFS may be (patho)physiologically relevant.

Spinal diffusion tensor tractography for differentiation of intramedullary tumor-suspected lesions.

BACKGROUND AND PURPOSE: Primary MRI diagnosis of spinal intramedullary tumor-suspected lesions can be challenging and often requires spinal biopsy or resection with a substantial risk of neurological deficits. We evaluated whether Diffusion Tensor Imaging (DTI) tractography can facilitate the differential diagnosis. MATERIALS AND METHODS: Twenty-five consecutive patients with an intramedullary tumor-suspected lesion considered for spinal surgery were studied with a Diffusion-weighted multi-shot read out segmented EPI sequence (RESOLVE). White matter tracts ("streamlines") were calculated using the FACT algorithm and visually co-registered to a T2-weighted 3D sequence. The fused images were assessed concerning spinal streamline appearance as normal, displaced or terminated. Definite diagnosis was verified by histological analysis or further clinical work-up. RESULTS: All patients with normal appearing streamlines (n=6) showed an acute inflammatory demyelinating pathology in the further clinical work-up. In 10 patients streamline displacing lesions were found from which 5 patients underwent a surgical treatment with histologically confirmed low-grade tumors like ependymomas and pilocytic astrocytomas. In nine patients streamlines were terminated, from which 6 patients received a histology proven diagnoses with a more heterogenous spectrum (3 cases of high grade tumor, 1 case of low grade tumor with intralesional hemorrhage and 2 cases with gliosis but no tumor cells). CONCLUSION: Using multi-shot DTI spinal tractography acute inflammatory lesions can be differentiated from other tumorous intramedullary lesions. The entity diagnosis of spinal tumors seems to be more challenging, primarily due to the variety of factors like invasivity, expansion or intralesional hemorrhage.

VHL c.505 T>C mutation confers a high age related penetrance but no increased overall mortality.

BACKGROUND: Germline mutations of the VHL gene cause von Hippel-Lindau syndrome (VHL). In southern Germany, a specific mutation in this gene, c.505 T>C, is one of the most frequent alterations owing to a founder effect. METHODS: This study was conducted to evaluate morbidity, specific clinical risk profile, and mortality among a series of VHL c.505 T/C mutation carriers. A total of 125 eligible subjects carrying VHL c.505 T/C underwent ophthalmoscopy and gadolinium enhanced magnetic resonance imaging of the brain, the spinal cord, and the abdomen. Age related penetrance, morbidity, and mortality were assessed. RESULTS: Frequently observed lesions were phaeochromocytoma (47%), retinal angiomas (36%), haemangioblastoma of the spine (36%), and haemangioblastoma of the brain (16%). Four patients developed renal cell carcinoma. VHL was symptomatic in 47% of subjects; 30% were asymptomatic despite the presence of at least one VHL related tumour and 23% of the carriers had no detectable VHL lesion. Of the 19 patients who had died (15%), 10 died of symptomatic VHL lesions. Overall penetrance by cumulative incidence functions is estimated at 48% by 35 years and 88% by 70 years. In contrast to the only existing published report based on patients with presumably unselected VHL germline mutations, the mortality rate for c.505 T/C mutation carriers is comparable to that of the general population of Germany. CONCLUSIONS: Our results are an important example that a specific genotype, at least in the case of VHL c.505 T/C, can favourably impact on mortality despite a high age related penetrance. Our study also indirectly provides objective data which might be useful to the life and health insurance industry; it would appear that c.505 T>C mutation positive subjects have similar disease specific mortality to that of the general population owing to a combination of phenotype and timely detection of mutation carrier status followed by aggressive clinical screening and, if necessary, treatment.

Clonal origin of recurrent meningiomas.

Meningiomas are common intracranial and intraspinal tumors. They are treated primarily by surgical resection. Meningioma recurrence following surgery is frequent despite advances in microneurosurgery. However, it is not clear whether recurrent meningiomas, close or distant to the primary resection site, arise from incomplete resection, dissemination of tumor fragments or from independent tumor growth. In order to address the question of clonality in recurring meningiomas, we examined a series of five patients with a total of 14 tumors for X-chromosome inactivation in the tumor tissues. Four patients with a total of 11 meningiomas were informative for polymorphisms either in the PGK or the AR genes. All recurrent meningiomas were found to be clonal with respect to the primary lesions. This finding suggests a common molecular pathogenesis of primary meningioma and subsequent recurrences (p<0.01). In a sixth patient, we analyzed the NF2 gene for mutations in the primary and 5 recurrent meningiomas. All six lesions carried the identical NF2 mutation, strongly indicating a common origin for these tumors. We conclude that recurrent meningiomas usually arise from dissemination of tumor fragments, most likely at the time of the first surgical resection. Our data should alert to the potential of meningioma cells for seeding during surgical procedures.

The autoinhibitory feedback control of acetylcholine release in human neocortex tissue.

Slices of human neocortex prelabelled with [3H]choline were superfused and stimulated electrically (3 Hz, 2 ms, 24 mA) in order to investigate the autoreceptor-mediated modulation of acetylcholine (ACh) release. The concentration-response curve of the muscarinic agonist oxotremorine (pKd = 6.76 +/- 0.06), which was equipotent to ACh, was shifted to the right in a parallel manner by atropine (pA2 = 8.56 +/- 0.11), as evaluated by non-linear regression analysis. Calculation of the biophase concentration of ACh showed that no ACh could be assumed to be present under these conditions, whereas following inhibition of the acetylcholinesterase by physostigmine (0.1 microM) a biophase concentration of 10(-6.89 +/- 0.11) M was estimated. The depression of ACh release due to physostigmine and tacrine, another anticholinesterase, was antagonized by atropine. When the autoinhibition was operative atropine and the M2 subtype specific muscarinic antagonists, AF-DX 116 and methoctramine, significantly increased the release of ACh whereas the 'facilitatory' effects of the M1 and M3-specific drugs, pirenzepine and hexahydrosiladifenidol, were not significant. Although different disinhibitory effects of the subtype-specific antagonists were found, they did, however, not show a pattern which would allow a clear characterisation of the subtype of muscarinic receptor associated with the autoreceptor. The release of ACh from neocortex tissue of the (non-demented) neurosurgical patients decreased with their age. This finding is consistent with the hypothesis that the normal aging process resembles a delayed and attenuated disease process of senile dementia of Alzheimer's type.(ABSTRACT TRUNCATED AT 250 WORDS)

5-HT1D-like receptors inhibit the release of endogenously formed [3H]GABA in human, but not in rabbit, neocortex.

Both human and rabbit brain contain the 5-hydroxytryptamine (5-HT)1D subtype of 5-HT1 receptors. We studied the effects of 5-HT1D receptor stimulation on neocortical [3H] gamma-aminobutyric acid (GABA) release from GABAergic neurons in these species. The 5-HT1D receptor agonist sumatriptan depressed [3H]GABA release in human neocortex and the 5-HT1 receptor antagonist metitepin prevented this depression with potencies suggesting mediation by 5-HT1D-like receptors. In rabbit neocortex, however, 5-HT1D agonists did not affect the release of [3H]GABA. Since 5-HT and GABA seem to function antagonistically in anxiety disorders their neocortical interaction may be (patho)physiologically relevant.

Extended preoperative polyvinyl alcohol microembolization of intracranial meningiomas: assessment of two embolization techniques.

PURPOSE: To evaluate the efficacy of preoperative meningioma devascularization with small polyvinyl alcohol (PVA) particles. METHODS: In 34 patients with intracranial meningiomas, CT, MR, 1H MR spectroscopy, MR volumetric measurements, intraoperative ultrasound, and histopathologic findings were used to compare the efficacy of two embolization techniques: 1) administration of 150- to 300-microns PVA particles in the usual suspension, and 2) administration of 50- to 150-microns PVA particles in a highly diluted suspension. RESULTS: Angiography after embolization demonstrated the total elimination of tumor blush in all patients. Contrast-enhanced MR after the administration of 150- to 300-microns PVA particles revealed a reduction of tumor enhancement in only two out of 14 patients. Only after the use of small particles could significant tumor necrosis be depicted on MR and confirmed histopathologically after surgery. In 12 of 20 patients, 30% to 95% of the whole tumor was necrotic with 17% to 20% reduction of tumor volume in four cases, leading to recovery from the initial neurologic deficits. In three of 20 patients without sufficient steroid medication before the treatment, tumor swelling occurred. Postembolization MR disclosed a tumor volume increase of 10% to 20% in these patients. 1H MR spectroscopy of the tumors showed an increase of lactate and aliphatic lipid compounds after embolization, indicating tumor infarction. Surgical removal of effectively embolized meningiomas without significant blood loss was possible. The appearance of the tumor at operation, ultrasound examination, and the histopathologic examination of different parts of the tumor confirmed the preoperative MR findings suggesting necrosis. CONCLUSION: Extended microembolization with 50- to 150-microns PVA particles improves the surgical treatment of meningiomas, as compared with larger particle embolization. It may also be the only treatment required in older or high-risk patients. The protective effect of steroid medication before the endovascular treatment of meningiomas is suggested by our study.

Exclusively intracranial cranial fasciitis in a child. Case report.

The authors present a case of an intracranial tumor in a 7-year-old girl leading to increasing hemiparesis. The lesion arose from the dura and consisted of fibroblasts in a myxoid matrix. The diagnosis of cranial fasciitis was made. The histological, immunohistological, and ultrastructural features of the tumor are described and the differential diagnosis is discussed.

Intramedullary spread of a cerebral oligodendroglioma.

A case of intramedullary spinal metastasis of a cerebral oligodendroglioma is presented. This exceptional presentation, as well as the routes of dissemination, are discussed by review of the literature.

Intraoperative ultrasound imaging: comparison of pathomorphological findings in US versus CT, MRI and intraoperative findings.

Since 1987, Ultrasound (US) is performed routinely as real time navigation system in our neurosurgical practice. In 374 cases with different pathologies the preoperative CT and MRI images were compared with the intraoperative US images and the operative findings. In all instances, the lesion could be localized and described in detail. US findings correlated with the findings an CT/MRI, concerning size and shape of lesions. US allowed the differentiation of more structural details within tissue compartments. The demarcation of gliomas was not as well defined in US as compared to CT/MRI, which correlated with the intraoperative situation. As for CT/MRI imaging, a correlation between US findings and histopathology of the lesion was not possible. In our opinion. intraoperative US imaging is an excellent tool for localization of cerebral and medullar lesions and for detailed description of their interior. This indicates a widespread applicability of this method in neurosurgery as an anatomical link between preoperative imaging and the reality of the operative field.

Intraoperative ultrasound imaging: practical applicability as a real-time navigation system.

Experience with the use of Intaoperative Ultrasound (US) imaging as real time navigation system in neurosurgery is presented and discussed. Since 1987 we have performed US routinely in a wide variety of intracerebral and intramedullar pathologies. In this analysis we define useful intraoperative applications. Accurate definition of deep-seated lesions and their delineation from surrounding anatomical structures is possible with an US frequency of 5 MHz. Small subcortically located lesions can clearly be visualized with a high frequency probe. Differentiation between solid tumor, cyst and necrosis can be delineated. Identification of residual tumor is difficult. Dural sinuses and eventual invading tumor can be visualized by a 10 MHz probe. US guidance can be helpful for puncturing with a catheter, needle or endoscope. Postoperative percutaneous US imaging through a burr hole did not prove to be useful. The intraoperative use of US imaging is a reliable method for determining the size, shape and localization of lesions. It can be used as a practicable, cost effective and timesaving real time navigation system.

Cervical myelopathy due to ossification of the posterior longitudinal ligament.

A case of cervical myelopathy due to ossification of the posterior longitudinal ligament is presented. This disease is rather frequent among Japanese, but rare among non-Mongolian persons. To our knowledge, this is the first published Belgian patient with a myelopathy. The clinical and radiographic data are discussed together with a review of the literature.

[Brain metastases. Possibilities and limits of treatment]. / Hirnmetastasen. Möglichkeiten und Grenzen der Behandlung.

The objective of the treatment of brain metastases is not merely to control the disease, but also to preserve an acceptable quality of life by keeping neurological symptoms in abeyance for as long as possible. In most cases, symptoms may be due to considerable perifocal edema. This is responsive to treatment with steroids, and these are therefore given to all patients. Specific treatment regimens include microsurgical removal of metastatic lesions, radiosurgery, irradiation of the brain, and chemotherapy. The choice of the treatment modality is dictated by the general state of health of the patient, the location and size of the metastases, the number of such lesions, and systemic involvement.

Freiburg neuropathology case conference: a midline mass lesion in an infant.

This article presents the case of a 10-month-old baby girl with an atypical teratoid/rhabdoid tumor. The differential diagnosis relied on the findings from magnetic resonance with T1 and T2-weighted imaging as well as histological and immunohistochemical methods. The characteristics of the possible candidate lesions considered for the differential diagnosis are described.

Free-hand bedside catheter evacuation of cerebellar hemorrhage.

OBJECT: Cerebellar hemorrhage is a life-threatening condition that requires immediate surgical intervention. Open craniectomy, hemorrhage evacuation and posterior fossa decompression is the treatment of choice. Patients with aspirin antithrombotic medication, however, face an increased risk of postoperative rebleeding, because it is impossible to normalize blood coagulation in time. To sufficiently treat these patients, we have developed a minimally-invasive, free-hand, bedside catheter evacuation technique. CLINICAL PRESENTATION: In a retrospective analysis, two patients with a mean age of 68 years and antithrombotic aspirin medication with cerebellar hemorrhage were treated. On admission, mean hemorrhage volume was 30.25 mL or 3.7x4.75x3.03 cm, mean GCS was 7.5, initial aspiration drained a mean 24 mL of blood. After a mean of 2.5 days of urokinase lysis, mean hemorrhage volume was 3.7 mL or 2.25x2.0x1.15 cm and mean EGOS on discharge was 4.5. After a mean follow-up of 408 days, the mean EGOS was 5.5, and both patients were alive. CONCLUSION: We conclude from these data that, in selected cases, bedside catheter placement and consequent urokinase lysis is a successful way to drain posterior fossa hemorrhage. However, experience in catheter positioning is crucial and the technique therefore should only be performed by experienced neurosurgeons.