Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation.

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

Spinal cord stimulation ameliorates neuropathic pain-related sleep disorders: a case series.

OBJECTIVE: Although sleep disorder is one of the most serious comorbidities of refractory chronic pain, it is usually assessed only from the patients' subjective point of view. Therefore, we aimed to objectively evaluate the sleep efficiency of patients with chronic pain. METHODS: Using an actigraph, a highly sensitive accelerometer, we assessed the sleep efficiency of six patients with chronic pain before and after the introduction of spinal cord stimulation (SCS). RESULTS: While pain improved in only five out of six patients after SCS, sleep efficiency improved in all cases. Interestingly, in one case, sleep efficiency improved even though pain intensity remained unchanged. CONCLUSION: With the use of an actigraph, improvements in sleep of patients with chronic pain undergoing SCS were demonstrated. One case showing improvement in sleep despite pain palliation may suggest that SCS might have independently affected the sleep system, although further studies are necessary.

Diagnosis and surgical strategy for sacral meningeal cysts with check-valve mechanism: technical note.

OBJECTIVE: There is agreement that symptomatic sacral meningeal cysts with a check-valve mechanism and/or large cysts representing space-occupying lesions should be treated surgically. This study investigated factors indicating a need for surgical intervention and surgical techniques for sacral meningeal cysts with a check-valve mechanism. METHODS: In ten patients presenting with sciatica and neurological deficits, myelography, computed tomography (CT) myelography, and magnetic resonance imaging (MR imaging) detected sacral meningeal cysts with a check-valve mechanism. One patient had two primary cysts. Ten cysts were type 2 and one cyst was type 1. Nine of the ten patients had not undergone previous surgery, while the remaining case involved recurrent cyst. For the seven patients with normal (i.e., not huge or recurrent) type 2 cysts and no previous surgery (eight cysts), suture after collapse of the cyst wall was performed. For the recurrent type 2 cyst, duraplasty and suture with collapse of the cyst wall were performed to eliminate the check-valve mechanism. For the remaining type 2 cyst, a primary root was sacrificed because of the huge size of the cyst. For the type 1 cyst, the neck of the cyst was ligated. RESULTS: In all cases, chief complaints disappeared immediately postoperatively and no deterioration of clinical symptoms has been seen after a mean follow-up of 27 months. CONCLUSIONS: The presence or absence of a check-valve mechanism is very important in determining the need for surgical intervention for sacral meningeal cysts.

Peripheral nerve field stimulation successfully manages axial pain after posterior cervical spine surgery: case report.

Axial neck and back pain after cervical spinal surgery is a common postoperative complication and can last for years. It is sometimes refractory to conventional treatments such as pharmacotherapy and spinal cord stimulation (SCS). Peripheral nerve field stimulation (PNFS) was recently introduced as an alternative treatment in the management of axial back pain into the occipital/craniofacial region and trunk in occipital neuralgia, post-herpetic neuralgia, and low back pain after lumbar spine surgery. However, PNFS has not been applied to axial neck pain. The patient suffered from occipital neuralgia and axial back pain after cervical spine surgery. In addition to PNFS of the greater occipital nerves for occipital neuralgia, we subcutaneously implanted two electrodes into the bilateral neck regions parallel with a sequential arrangement of the cervical spine. The electrodes were placed immediately above the trapezius muscles and electrical paresthesia was enhanced by posterior neck muscle twitches, fully covering the areas with axial neck pain. Both electrodes successfully achieved an almost 70% decrease in occipital and axial neck pain. Since axial neck pain after cervical spinal surgery often affects patients' health-related quality of life, neuromodulation in the form of PNFS may have the potential to become a novel alternative to conventional pain treatments for medically refractory axial neck pain.

Successful surgical strategy for ventral thoracic spinal perimedullary spinal arteriovenous fistulas: Case report.

BACKGROUND: Spinal arteriovenous fistulas (AVFs) are vascular lesions that often pose significant surgical challenges. This is particularly true for those located close to the anterior spinal artery. Here, we analyzed the surgical options for treating an anterior perimedullary AVF (pAVFs). CASE DESCRIPTION: A 66-year-old male with the right lower extremity weakness was diagnosed with a spinal dural AVF at the L1 level. It was initially treated with open surgery followed by CyberKnife radiosurgery at another institution. Five years later, he presented with a persistent pAVF fistula now involving the T11 level; the major feeder originated on the left at the T7-T8 level (e.g., involving a left-sided "duplicated" anterior spinal artery). Utilizing a three-dimensional (3D) computer tomography (CT) guided approach; he underwent a left-sided posterolateral T10-T12 laminectomy, sufficient to allow for 30-40° of anterior spinal cord rotation. This was performed under neurophysiological monitoring without any significant changes. Surgery included indocyanine green video angiography, temporary feeder clipping, and complete occlusion of the AVF, followed by complete clipping/resection as confirmed on postoperative magnetic resonance imaging. CONCLUSION: Utilizing a 3D CT image, a ventral pulmonary arteriovenous malformation was excised utilizing a left-sided posterolateral approach allowing for 30-40° of cord rotation.

In Vivo Volume Dynamics of Dendritic Spines in the Neocortex of Wild-Type and Fmr1 KO Mice.

Excitatory synapses are often formed at small protrusions of dendrite, called dendritic spines, in most projection neurons, and the spine-head volumes show strong correlations with synaptic connectivity. We examined the dynamics of spine volume in the adult mouse visual cortex using time-lapse in vivo two-photon imaging with a resonant Galvano scanner. Contrary to expectations, we found that the spines in the adult neocortex showed fluctuations to a similar degree as that observed in young hippocampal preparations, but there were systematic differences in how the dynamics were dependent on spine volumes, thus allowing for fewer fluctuations in small spines, which could account for the relatively low turnover rates of neocortical spines in vivo. We found that spine volumes fluctuated to a greater extent in a mouse model (Fmr1 knockout) of fragile X mental retardation than in wild-type mice, and the spine turnover rates were also higher in Fmr1 knock-out mice. Such features of spine dynamics in Fmr1 knock-out mice could be represented by a single slope factor in our model. Our data and model indicate a small but significant change in the average spine volume and more eminent differences in the statistical distribution in Fmr1 knock-out mice even in adulthood, which reflects the abnormal in vivo dynamics of spine volumes.

Calcineurin knockout mice show a selective loss of small spines.

Calcineurin is required for long-term depression and activity-dependent spine shrinkage, and calcineurin mutations have been identified in patients with schizophrenia. Moreover, mice with conditional knockout of calcineurin B (CNB-KO) exhibit behavioral abnormalities suggestive of schizophrenia. Changes in the dendritic spines of these mice, however, have not been investigated. We therefore examined the dendritic spines of CNB-KO mice, and observed a significant reduction in small spines and an increase in large spines in the prefrontal and visual cortices. The effect of CNB-KO on the spine sizes was relatively moderate, possibly due to the presence of spontaneous fluctuations (dynamics) in the dendritic spines themselves. Thus, CNB-KO mice showed a spine phenotype similar to those recently reported in patients with schizophrenia.

A huge presacral Tarlov cyst. Case report.

Perineural cysts have become a common incidental finding during lumbosacral magnetic resonance (MR) imaging. Only some of the symptomatic cysts warrant treatment. The authors describe the successful operative treatment of a patient with, to the best of their knowledge, the largest perineural cyst reported to date. A 29-year-old woman had been suffering from long-standing constipation and low-back pain. During an obstetric investigation for infertility, the clinician discovered a huge presacral cystic mass. Computed tomography myelography showed the lesion to be a huge Tarlov cyst arising from the left S-3 nerve root and compressing the ipsilateral S-2 nerve. The cyst was successfully treated by ligation of the cyst neck together with sectioning of the S-3 nerve root. Postoperative improvement in her symptoms and MR imaging findings were noted. Identification of the nerve root involved by the cyst wall, operative indication, operative procedure, and treatment of multiple cysts are important preoperative considerations.

Spinal extradural arteriovenous fistulas with retrograde intradural venous drainage: Diagnostic features in digital subtraction angiography and time-resolved magnetic resonance angiography.

Spinal extradural arteriovenous fistulas (AVFs) may be more difficult to prospectively identify than dural AVFs because they are less common than dural AVFs. The primary purpose was to further characterize the diagnostic imaging of spinal extradural AVFs with intradural retrograde venous drainage. The magnetic resonance (MR) imaging and angiographic results of 23 patients with suspected spinal dural AVFs were analyzed in order to distinguish dural and extradural AVFs. The diagnostic accuracy of MR angiography was retrospectively compared between dural and extradural AVFs. All 23 patients showed high intensity in the spinal cord on T2-weighted MR images. Eighteen out of 23 patients were diagnosed with dural AVFs, while the remaining 5 were diagnosed with extradural AVFs by angiography. Extradural AVFs were fed by a branch of the segmental artery to the vertebral body, characterized by a fistula located in the ventral extradural space, and drained retrogradely via an epidural venous pouch into intradural veins. The segmental artery was localized within 1 vertebral level using MRA in 12 out of 18 patients (67%) with dural AVFs and in 1 out of 5 patients (20%) with extradural AVFs (p=0.09). The reasons behind the lower accuracy was mainly the image misinterpretation. Congestion of the spinal cord in spinal extradural AVFs with intradural retrograde venous drainage was similar to that in dural AVFs, whereas its angioarchitecture differed from that of dural AVFs. A clearer understanding of the imaging features of extradural AVFs is important for improving the diagnostic accuracy and clarifying treatment targets.

Seismic evidence for flow in the hydrated mantle wedge of the Ryukyu subduction zone.

It is widely accepted that water-rich serpentinite domains are commonly present in the mantle above shallow subducting slabs and play key roles in controlling the geochemical cycling and physical properties of subduction zones. Thermal and petrological models show the dominant serpentine mineral is antigorite. However, there is no good consensus on the amount, distribution and alignment of this mineral. Seismic velocities are commonly used to identify antigorite-rich domains, but antigorite is highly-anisotropic and depending on the seismic ray path, its properties can be very difficult to distinguish from non-hydrated olivine-rich mantle. Here, we utilize this anisotropy and show how an analysis of seismic anisotropy that incorporates measured ray path geometries in the Ryukyu arc can constrain the distribution, orientation and amount of antigorite. We find more than 54% of the wedge must consist of antigorite and the alignment must change from vertically aligned to parallel to the slab. This orientation change suggests convective flow in the hydrated forearc mantle. Shear wave splitting analysis in other subduction zones indicates large-scale serpentinization and forearc mantle convection are likely to be more widespread than generally recognized. The view that the forearc mantle of cold subduction zones is dry needs to be reassessed.

Successful surgical strategy for a cervical hemangioblastoma: Case report.

BACKGROUND: Hemangioblastomas are hypervascular lesions and hence their surgical management is challenging. In particular, if complete resection is to be attained, all feeding and draining vessels must be occluded. Although most intramedullary spinal cord tumors are treated utilizing a posterior approach, we describe an anterior surgical strategy for resection of an intramedullary cervical hemangioblastoma. CASE DESCRIPTION: A 36-year-old female with a spinal hemangioblastoma located in the anterior cervical spinal cord presented with a long-standing history of motor weakness of the right upper extremity. Magnetic resonance imaging revealed a large multilevel extensive syrinx and a focal intramedullary enhanced tumor at the C6 level. Angiography showed that the main feeder to the tumor was the left radicular artery (C8), which originated from the thyrocervical trunk, penetrated the dura mater, and branched both rostrally and caudally into the anterior spinal artery (ASA). Three-dimensional computer graphic images showed the tumor was located in the anterior part of the spinal cord, adjacent to and supplied by the ASA. The planned anterior surgical approach involved a total corpectomy of C6 and partial corpectomies of C5 and C7. The tumor was entirely removed despite multiple adhesions, and was successfully freed from the ASA. Patency of the ASA was confirmed utilizing intraoperative indocyanine green videoangiography. Intraoperatively, no monitoring changes were encountered. The pathological diagnosis was of a hemangioblastoma. No postoperative deficit occurred. CONCLUSIONS: An anterior approach for the resection of an anteriorly located intramedullary spinal hemangioblastomas was successfully accomplished in this case.

Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo.

Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.

Rheumatoid leptomeningitis: rare complication of rheumatoid arthritis.

Rheumatoid leptomeningitis is a rare complication of rheumatoid arthritis (RA). We describe a woman with rheumatoid leptomeningitis presenting with acute-onset behavioral changes and consciousness disturbance in the early stage of RA. On fluid-attenuated inversion recovery images or diffusion-weighted images, high-signal-intensity lesions in the subarachnoid spaces of the right frontal lobe were observed. Biopsies of brain tissues and the dura mater located in the right frontal lobe were obtained. On the basis of the findings of histopathological analysis, a diagnosis of necrotizing granulomas involving the leptomeninges consistent with rheumatoid leptomeningitis was made. An early diagnosis of rheumatoid leptomeningitis and immediate initiation of treatment may prevent neurological sequelae.