Mobilization of the Anterior Inferior Cerebellar Artery When Firmly Adherent to the Petrous Dura Mater-A Technical Nuance in Retromastoid Transmeatal Vestibular Schwannoma Surgery: 3-Dimensional Operative Video.

The anterior inferior cerebellar artery (AICA) usually runs loosely within the cerebellopontine cistern; in rare cases, however, it is firmly adherent to the petrous dura mater.1,2 Recognizing this variation is particularly important in vestibular schwannoma surgery via the retrosigmoid transmeatal approach to prevent the high morbidity associated with vascular injury. This video demonstrates a surgical technique to effectively mobilize the AICA when firmly adherent to the petrous dura mater. A 39-year-old man presented with a history of progressive right-sided hearing loss without facial weakness or other associated symptoms3. Magnetic resonance imaging (MRI) demonstrated an intracanalicular lesion, suggestive of vestibular schwannoma. During follow-up, audiometry confirmed a further slight deterioration of hearing and repeated MRI demonstrated tumor growth (T2 according to Hannover classification). Since the patient opted against radiosurgery, a retrosigmoid transmeatal approach under continuous intraoperative monitoring was performed in supine position. Following drainage of cerebrospinal fluid and exposure of the cerebellopontine cistern, the AICA was found to be firmly adherent to the petrous dura mater. Both structures were elevated conjointly and displaced medially for safe drilling of the inner auditory canal, sufficient exposure, and complete excision of the vestibular schwannoma. The patient had an excellent recovery, hearing and facial function were preserved, and no secondary neurological deficits noted.The patient consented to publication of this anonymized video.

The role of intraoperative neuromonitoring in adults with Chiari I malformation.

OBJECT: Suboccipital decompression and duraplasty is considered the treatment of choice for Chiari-I-malformation. Several studies have shown improvement of neurophysiological parameters during decompressive surgery in pediatric patients. However, there is no evidence of the beneficial role of intraoperative neuromonitoring in adults. METHODS: A total of 39 consecutive patients (25 female, age 41.1±14.5 years [mean±SD]) underwent suboccipital decompression for the treatment of symptomatic Chiari-I-malformation senior neurosurgeon and his team. Continuous intraoperative monitoring of somatosensory-evoked potentials of the median nerve (m-SSEPs) and the posterior tibial nerve (t-SSEPs) and motor-evoked potentials to the hand (APB-MEPs) and foot (TA-MEPs) were applied to all patients, alone or in combination. The m-SSEP-N20, t-SSEP-P40, APB-MEP and TA-MEP amplitudes and latencies were recorded at the beginning of the surgery (baseline) and after dura closure. Neurological assessments of the patient were performed prior to surgery, after surgery and during each follow-up visit (3, 6 and 12 months). RESULTS: There was no significant change in m-SSEP-N20, t-SSEP-P40 or APB-MEP and TA-MEP amplitudes or latencies between the baseline and final measurements (p>0.05, Student's t-test). The average time between both recordings was 125±48min (mean±SD). Postoperatively, none of the patients presented new neurological deficits. During the mean follow-up period of 22.4±20.3 months, 92.6% of the symptoms improved or remained stable. Three patients (8.1%) exhibited a relapse of symptoms after 25.7±7.6 months, and only one patient (2.5%) needed secondary decompression after 24 months. CONCLUSION: Intraoperative neuromonitoring (INM) during the primary treatment of Chiari-I-malformation shows only subtle non-significant changes in SSEPs/MEPs without clinical correlation during suboccipital decompression. INM is not considered a prerequisite for a safe suboccipital decompression when operated by an experienced surgical team.

The value of dynamic radiographic myelography in addition to magnetic resonance imaging in detection lumbar spinal canal stenosis: A prospective study.

OBJECTIVE: MRI is regarded as the study of choice in the diagnosis of lumbar spinal stenosis. In some cases, the supine MRI leads to a misdiagnosis in the extent of lumbar spinal stenosis. Dynamic myelography can detect lumbar spinal stenosis in these cases of where the MRI may not be as sensitive. To compare the sensitivities of dynamic radiographic myelography and supine MRI in lumbar canal stenosis (LCS) patients and to determine whether dynamic radiographic myelography is a valuable diagnostic exam in the work-up of lumbar canal stenosis. PATIENTS & METHODS: Over two years, the imaging data of 100 consecutive patients who were suspected of having LCS were prospectively analyzed. All lumbar intervertebral segments were evaluated in each patient on sagittal MR T2-weighted images and lateral plane images by myelography using a semi-quantitative scoring system. The differences in scores for 5 motion segments under 3 conditions (supine MRI, upright sitting myelography and standing myelography with extension) were analyzed statistically. RESULTS: Of 100 patients with 500 analyzed intervertebral segments, 23 patients with inconclusive supine MRI results had LCS in standing myelography with extension. Compared with upright sitting myelography and supine MRI, standing myelography with extension yielded the highest score for every segment from L1/2 to L5/S1. Compared with the upright sitting myelography position, 61 more patients received a diagnosis of lumbar stenosis in the standing myelography with extension position, and 121 more stenotic segments were diagnosed. Compared with the supine MRI position, standing myelography with extension detected 64 more stenotic patients and 137 more stenotic segments. CONCLUSIO: n Based on a large patient sample, dynamic myelography is a valuable diagnostic tool in detecting lumbar spinal stenosis. Patients with lumbar spinal stenosis may have inconclusive supine MRI in 23% of cases being misdiagnosed as normal. This missed rate of LCS patients with unclear supine MRI results can be avoided with dynamic myelography. The combination of supine MRI and dynamic myelography is critical in the evaluation of LCS, especially if multisegmental findings are detected.

Detection and quantification of apoptosis in primary cells using Taqman® protein assay.

There are several methods to detect apoptosis using cleaved caspase-3 and each harbors its own advantages and disadvantages. When primary cell cultures are used, the disadvantages of the standard methods can make apoptosis detection difficult due to their slow growth rate and replicative senescence, thereby limiting the available cell number and experiment time span. In this chapter, we describe apoptosis detection and quantification using an innovative method named TaqMan(®) protein assay. TaqMan(®) protein assay uses antibodies and proximity ligation for quantitative real-time PCR. Biotinylated antibodies are labeled with oligonucleotides. When the labeled antibodies bind in close proximity, the oligonucleotides are connected using DNA ligase. The ligation product is amplified and detected using Taqman(®) based Real-Time PCR. Using this technique, we can not only detect apoptosis with a 1,000-fold higher sensitivity than western blot, but we can also exactly quantify cleaved caspase-3 expression. Thereby apoptosis can be determined and quantified in a fast reliable manner.

Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

Late neurological sequelae due to brainstem irradiation for an assumed glioma.

PURPOSE: There is ongoing discussion whether radiotherapy might be beneficial in the treatment of intracranial cavernomas, however long-term sequelae due to brainstem irradiation may exist. CASE REPORT: The case of a 72-year-old female is reported who received radiotherapy in the pre-MRI era due to a suspected intra-axial pontine lesion. Later on she developed severe trigeminal neuropathy and an MRI was performed 27 years after irradiation of the brainstem. On these images a large cavernous malformation with signs of multiple haemorrhages instead of the pontine glioma was seen accompanied by a substantial atrophy of brainstem structures. CONCLUSION: This case impressively demonstrates the long-term outcome of brainstem irradiation and reflects that cavernomas do not respond to radiotherapy.

Comparing the expression of integrins αvß3, αvß5, αvß6, αvß8, fibronectin and fibrinogen in human brain metastases and their corresponding primary tumors.

AIMS: To evaluate the expression of αv-series integrins in brain metastases. Inhibitors targeting these integrins are being tested for their therapeutic potential. MATERIAL AND METHOD: The extracellular regions of the αvß3, αvß5, αvß6, αvß8, the cytoplasmic domain of ß3, the αv-chain, and the ECM molecules fibronectin and fibrinogen were studied immunohistochemically in a series of 122 carcinoma and 60 melanomas metastatic to the central nervous system. In addition, 38 matched primary and metastatic tumors to the brain were compared directly. RESULTS: The αv-subunit was generally moderately to highly expressed in most tumors. αvß3 and cytoplasmic ß3 were weakly to moderately detectable in metastatic renal cell carcinomas and melanomas, αvß5 was prominently expressed in metastatic renal and colorectal carcinomas, αvß6 was most abundantly detectable in metastatic lung adenocarcinomas, but absent in melanomas. The tumor associated vessels in CNS metastases consistently expressed αvß3, αvß5, αv-, fibronectin and fibrinogen, however, mostly at low levels, while αvß6, αvß8 were lacking in vasculature. The comparative analysis of 38 matched primary tumors and brain metastases showed comparable levels of expression only for αvß3 and αvß8, while αvß6 and αvß5 were higher in primaries. CONCLUSION: We confirmed that integrin expression exhibits considerable heterogeneity according to tumor origin. αvß5 is the most promising target for integrin targeted treatment in brain metastases.

Primary cerebral low-grade B-cell lymphoma, monoclonal immunoglobulin deposition disease, cerebral light chain deposition disease and "aggregoma": an update on classification and diagnosis.

BACKGROUND: This work aims to add evidence and provide an update on the classification and diagnosis of monoclonal immunoglobulin deposition disease (MIDD) and primary central nervous system low-grade lymphomas. MIDD is characterized by the deposition of light and heavy chain proteins. Depending on the spatial arrangement of the secreted proteins, light chain-derived amyloidosis (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD). We present a case of an extremely rare tumoral presentation of LCDD (aggregoma) and review the 3 previously published LCDD cases and discuss their presentation with respect to AL. CASE PRESENTATION: A 61-year-old woman presented with a 3½-year history of neurologic symptoms due to a progressive white matter lesion of the left subcortical parieto-insular lobe and basal ganglia. 2 former stereotactic biopsies conducted at different hospitals revealed no evidence of malignancy or inflammation; thus, no therapy had been initiated. After performing physiological and functional magnetic resonance imaging (MRI), the tumor was removed under intraoperative monitoring at our department. Histological analysis revealed large amorphous deposits and small islands of lymphoid cells. CONCLUSION: LCCD is a very rare and obscure manifestation of primary central nervous system low-grade lymphomas that can be easily misdiagnosed by stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite result, a "wait-and-see" strategy can delay possible therapy for this disease. The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously remains controversial because of the low number of relevant cases.

Detection and quantification of farnesol-induced apoptosis in difficult primary cell cultures by TaqMan protein assay.

Apoptosis can be detected reliably by assaying for cleaved caspase-3, for which active caspase-3 antibodies are used in several methods, such as immunocytochemistry, enzyme-linked immunosorbent assay, and western blot. In this study, we used TaqMan protein assay (TPA), a novel method for protein detection and quantification that detects proteins by amplification of substitute DNA templates. TPA uses antibodies and proximity ligation for quantitative real-time PCR. Meningiomas are primarily benign intracranial tumors. Primary cell cultures of meningiomas are often unsuitable for sensitive protein detection methods. We optimized a TPA to detect active caspase-3 and evaluated its ability to detect farnesol-induced apoptosis in primary meningioma cells. The specificity and sensitivity of the inactive and active caspase-3 assay were determined using recombinant caspase-3. Apoptosis was induced in meningiomas in the presence of 0.2 µM farnesol as shown by immunocytochemistry of single-stranded DNA. Also, viability decreased by over 90 % after treatment with 1.2 µM farnesol for 24 h. The TPA detected a significant increase in active caspase-3 after treatment with 2 and 4 µM farnesol for 2 h, which could not be detected using standard methods such as western blot and immunofluorescence. In addition, TPA determined that meningiomas show disparate sensitivities to low concentrations of farnesol. Caspase-3 expression fell significantly in cells that were treated with 0.25 µM farnesol for 2 h. Further, by TPA, active caspase-3 peaked after 2 h and declined with longer incubation times. This study demonstrates that cleaved caspase-3 is detected and quantified reliably in meningiomas by TPA.

Meningiomas, nerve sheath tumors, and pituitary tumors: diagnosis and treatment.

This article gives an overview of meningiomas, pituitary tumors, and intracranial nerve sheath tumors as regards epidemiology, diagnosis, and treatment. Discussion includes the definition of these tumors and their symptomatology, diagnostic procedures, treatment options, surgical techniques, and outcomes.

Biological motion processing: the left cerebellum communicates with the right superior temporal sulcus.

The cerebellum is thought to be engaged not only in motor control, but also in the neural network dedicated to visual processing of body motion. However, the pattern of connectivity within this network, in particular, between the cortical circuitry for observation of others' actions and the cerebellum remains largely unknown. By combining functional magnetic resonance imaging (fMRI) with functional connectivity analysis and dynamic causal modelling (DCM), we assessed cerebro-cerebellar connectivity during a visual perceptual task with point-light displays depicting human locomotion. In the left lateral cerebellum, regions in the lobules Crus I and VIIB exhibited increased fMRI response to biological motion. The outcome of the connectivity analyses delivered the first evidence for reciprocal communication between the left lateral cerebellum and the right posterior superior temporal sulcus (STS). Through communication with the right posterior STS that is a key node not only for biological motion perception but also for social interaction and visual tasks on theory of mind, the left cerebellum might be involved in a wide range of social cognitive functions.

Selective enrichment of hypericin in malignant glioma: pioneering in vivo results.

Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher in C6 glioma as compared to normal tissue. Maximum hypericin uptake was achieved at 24 h after injection. Ratios of fluorescence intensity between tumor and normal tissue as well as infiltration zone and normal tissue of about 6.1:1 and 1.4:1 were found. Considering tissue auto-fluorescence, fluorescence ratios of about 19.8:1 and 2.5:1 were calculated, respectively. Therefore, hypericin seems to be quite an effective fluorescence marker for the detection of glioma in vivo. To the best of our knowledge, the present study demonstrates for the first time that hypericin accumulates selectively in intracerebral implanted C6 glioma in vivo after systemic (intravenous) administration.

Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor.

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid-induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence-guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence-guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380-430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.

The first 50s: can we achieve acceptable results in vestibular schwannoma surgery from the beginning?

OBJECTIVE: Vestibular schwannoma surgery requires a profound knowledge of anatomy and long-standing experience of surgical skull base techniques, as patients nowadays requests high-quality results from any surgeon. This educes a dilemma for the young neurosurgeon as she/he is at the beginning of a learning curve. The presented series should prove if surgical results of young skull base surgeons are comparable respecting carefully planned educational steps. METHODS: The first 50 vestibular schwannomas of the first author were retrospectively evaluated concerning morbidity and mortality with an emphasis on functional cranial nerve preservation. The results were embedded in a timeline of educational steps starting with the internship in 1999. RESULTS: Fifty vestibular schwannomas were consecutively operated from July 2007 to January 2010. According to the Hannover Classification, 14% were rated as T1, 18% as T2, 46% as T3, and 21% as T4. The overall facial nerve preservation rate was 96%. Seventy-nine percent of patients with T1-T3 tumours had no facial palsy at all and 15% had an excellent recovery of an initial palsy grade 3 according to the House & Brackman scale within the first 3 months after surgery. Hearing preservation in T1/2 schwannomas was achieved in 66%, in patients with T3 tumours in 56%, and in large T4 tumours in 25%. Three patients suffered a cerebrospinal fluid fistula (6%), and one patient died during the perioperative period due to cardiopulmonary problems (2%). CONCLUSIONS: The results demonstrate that with careful established educational plans in skull base surgery, excellent clinical and functional results can be achieved even by young neurosurgeons.

Step-by-step education of the retrosigmoid approach leads to low approach-related morbidity through young residents.

BACKGROUND: Neurosurgery requires a profound knowledge of anatomy and surgical skills. The skull base approach is the crucial step for successful intradural performance. Resident training at experienced institutions must consider this background when educating young neurosurgeons. METHODS: From 2006-2008, 223 retrosigmoid approaches for various cerebellopontine angle pathologies have been performed at the Department of Neurosurgery Eberhard-Karls-University, Tübingen. After a minimum time of 6 months assisting, followed by participation of dissection courses and continuous anatomical training, later performing their first approaches under direct supervision of an experienced surgeon, residents perform their first retrosigmoid approaches autonomously in the operating theatre. With this study, we evaluate the surgical morbidity and the time factor related to the educational level of the surgeon. RESULTS: Comparing surgical-related morbidity between approaches performed by experienced neurosurgeons (>100 procedures) and young residents (<20 procedures), we found no significant differences concerning the incidence of cerebrospinal fluid fistulae, sinus lacerations, wound infections, cranioplasty dislocations, or occipital nerve neuromas. Even the mean time for the procedure (positioning, time-to-dural incision) was not significantly longer in the trainee group. CONCLUSION: Respecting the stepwise educational levels for skull base surgery, including microanatomical studies, educational courses, and expert guidance at surgery, the retrosigmoid approach can be performed by young residents without increased morbidity at experienced institutions.

Cerebellar engagement in an action observation network.

The cerebellum has traditionally been viewed as a brain structure subserving skilled motor behaviors. However, the cerebellum might be involved not only in movement coordination, but also in action observation and understanding of others' actions. Veridical visual perception of human body motion is of immense importance for a variety of daily-life situations and for successful social interactions. Here, by combining visual psychophysics with a lesion analysis, we assessed visual sensitivity to human walking in patients with lesions to the left cerebellum. Patients with left lateral cerebellar lesions exhibit deficits in visual sensitivity to body motion, whereas medial lesions do not substantially affect visual perception of human locomotion. The findings point to left lateral cerebellar involvement in an action observation network. We discuss possible mechanisms of cerebellar engagement in visual social perception revealed by body motion.

Defining the line between hydromyelia and syringomyelia. A differentiation is possible based on electrophysiological and magnetic resonance imaging studies.

PURPOSE: With the frequent use of magnetic resonance imaging (MRI), patients with subtle and diffuse symptoms due to small syrinx cavities increasingly present to neurosurgical care. In this respect, a dilated central canal, hydromyelia, must be separated from patients with true syringomyelia with an underlying disorder, as they do not share clinical and radiological features. We hypothesize that a differentiation of these two entities with distinct diagnostic tools is possible. METHODS: To describe the entity of hydromyelia, we excluded all patients from the syringomyelia database (n = 142) with any obvious cause of a syringomyelia, any objective neurological deficits on clinical examination, pathological results on electrophysiological monitoring (SSEP, MEP, silent periods) or a widening of the spinal cord cavity of more than 6 mm on MRI [routine acquisitions with FLAIR, T1/T2-weighted images, Cine and CISS (constructive interference in steady-state) studies]. Life quality was assessed through SF-36 questionnaires and an individualized questionnaire for the clinical history, pain and alternative therapies. RESULTS: Forty patients (15 males/25 females) matched the criteria of a hydromyelia. With a mean age of 36.7 years (range 11-62), they almost all presented with pain (79%) or dysaesthesia of the limbs, with some having been an incidental finding (10%). Over a follow-up time of 36.9 months (range 6-93) there was no neurological or radiological deterioration. CONCLUSIONS: Patients with a hydromyelia do not share clinical or radiological characteristics with patients harbouring a true syringomyelia. As hydromyelia does not represent a disease with an underlying pathology, no clinical or radiological progression has been seen. With sophisticated diagnostic tools to rule out any pathology this subset of patients can be identified.

Resection of malignant brain tumors in eloquent cortical areas: a new multimodal approach combining 5-aminolevulinic acid and intraoperative monitoring.

OBJECT: Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. METHODS: Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. RESULTS: Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. CONCLUSIONS: The authors' first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.