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.

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.

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.

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.

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.

[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.

Late bacterial granuloma at an intrathecal drug delivery catheter.

In the case reported, neurological complaints were pain and dysaesthesiae in the lower back and thigh, as well as paresis of the ileopsoas muscle. MRI of the lumbar spine showed an intradural-extramedullary mass at the level of L1 homogeneously enhancing with gadolinium. This mass was situated at the tip of an intrathecal catheter implanted 11 years before for a morphine trial infusion as therapy for phantom pain after amputation of the right arm. Now, removal of the catheter was performed. Cultures of lumbar CSF and the catheter tip demonstrated coagulase negative staphylococcus. Antibiotic medication with cephalosporines was given for 6 weeks. After removal of the catheter, the patient was free of pain and he progressively regained full neurological function. Although most catheter-associated granulomas reported so far were sterile in nature, bacterial infection should still be considered even years after catheter placement.

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.

Benefits and limitations of image guidance in the surgical treatment of intracranial dural arteriovenous fistulas.

BACKGROUND: Despite major advances in endovascular embolization techniques, microsurgical resection remains a reliable and effective treatment modality for dural arteriovenous fistulas (DAVF). However, intraoperative detection of these lesions and identification of feeding arteries and draining veins can be challenging. In a series of 6 patients who were not candidates for definitive treatment by endovascular embolization we evaluated the benefits and limitations of computer-assisted image guidance for surgical ablation of DAVF. METHODS: Of the 6 patients, 5 presented with haemorrhage and one with seizures. Diagnosis of DAVF was made by conventional angiography and dynamic contrast enhanced MR angiography (CE-MRA). All patients were surgically treated with the assistance of a 3D high resolution T1-weighted MR data set and time-of-flight MR angiography (MRA) obtained for neuronavigation. Registration was based on cranial fiducials and image-guided surgery was performed with the navigation system. FINDINGS: Four of the 6 patients suffered from DAVF draining into the superior sagittal sinus, one fistula drained into paracavernous veins adjacent to the superior petrosal sinus and one patient had a pial fistula draining in the straight sinus. DAVF diagnosed with conventional angiography could be located on CE-MRA and MRA prior to surgery. MRI and MRA images were combined on the neuronavigation workstation and DAVF were located intraoperatively by using a tracking device. In 4 out of 6 cases neuronavigation was used for direct intraoperative identification of DAVF. Brain shift prevented direct tracking of pathological vessels in the other 2 cases, where navigation could only be used to assist craniotomy. Microsurgical dissection and coagulation of the fistulas led to complete cure in all patients as confirmed by angiography. CONCLUSIONS: Neuronavigation may be used as an additional tool for microsurgical treatment of DAVF. However, in this small series of 6 cases, surgical procedures have not been substantially altered by the use of the neuronavigation system. Image guidance has been beneficial for the location of small, superficially located DAVF, whereas a navigated approach to deep-seated lesions was less accurate due to the familiar problem of brain shift and brain retraction during surgery.

Subarachnoid haemorrhage due to cervical spinal cord haemangioblastomas in a patient with von Hippel-Lindau disease.

A case is presented with severe infra- and supratentorial subarachnoid haemorrhage (SAH) caused by intramedullary haemangioblastomas of the cervical spinal cord. The patient initially had a typical SAH symptomatology without neurological deficit. The cerebral angiogram was nondiagnostic. After admission the patient developed slightly progressive right sensorimotor paresis. Angiography of the cervical spine and MRI delineated three intramedullary haemangioblastomas. Retrospectively the diagnosis of von Hippel-Lindau (VHL) disease was made by multiple haemangioblastomas and a positive family history. The three lesions were surgically completely removed.

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.

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.

[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.

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.

Neurosurgical interventions in children with Maroteaux-Lamy syndrome. Case report and review of the literature.

This paper reports the case of a 14-year-old child with Maroteaux-Lamy syndrome (mucopolysaccharidosis type 6) who was treated consecutively for compressive damage of the optic nerves, hydrocephalus communicans and progressive spastic tetraparesis within 2 years. The clinical course of the patient is presented and the pathophysiologic mechanisms of disease progression in patients with Maroteaux-Lamy syndrome are discussed and reviewed.

Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system.

OBJECTIVES: Cerebellar haemangioblastoma occurs sporadically or as a component tumour of autosomal dominant von Hippel-Lindau disease. Biallelic inactivation of the VHL tumour suppressor gene, which is located on chromosome 3p, has been shown to be involved in the pathogenesis of both tumour entities. Mechanisms of VHL inactivation are intragenic mutations, mitotic recombination events, and hypermethylation of the promoter region. The systematic and complete examination of these genetic and epigenetic phenomena in large series of von Hippel-Lindau disease related and sporadic hemangioblastomas has, thus far, not been performed. METHODS: In the largest series to date, 29 von Hippel-Lindau disease associated and 13 sporadic haemangioblastomas were investigated for all suggested inactivating mechanisms of the VHL gene using single strand conformational polymorphism (SSCP), loss of heterozygosity (LOH), and methylation analyses. Additionally, corresponding blood samples of all patients were screened for VHL germline mutations by SSCP and Southern blotting. RESULTS: Germline mutations were identified in 94% of patients with von Hippel-Lindau disease and their tumours and 62% of these hemangioblastomas showed LOH of chromosome 3p. Of the 13 sporadic tumours, 23% showed a single somatic mutation of the VHL gene that was not present in the germline. 3p LOH was identified in 50% of informative sporadic tumours. No von Hippel-Lindau disease related or sporadic tumour demonstrated VHL promoter hypermethylation. CONCLUSIONS: For most von Hippel-Lindau disease related haemangioblastomas, the inactivation or loss of both alleles of the VHL gene, as predicted by the Knudson two hit theory, is required. However, in a subset of tumours including most sporadic haemangioblastomas, the genetic pathways involved in tumorigenesis have yet to be defined and may represent alterations of a different pathway or pathways.