Primary epidural lymphocyte-depleted Hodgkin’s lymphoma of the thoracic spine – presentation of a rare disease variant

Background: Lymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for < 1% of all cases. Patients often have advanced-stage disease at the time of presentation with an aggressive clinical course. Even more uncommon is primary extranodal disease and rarely it will be presenting with spinal cord compression. Case presentation: An 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome. Conclusion: To the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy

Pre-Surgical and Surgical Planning in Neurosurgical Oncology - A Case-Based Approach to Maximal Safe Surgical Resection in Neurosurgery

Use of functional neuroimaging capabilities such as fMRI, DTI, MRP, MRS, AS-PET-CT, SPECT, and TMS as noninvasive tools to visualize intrinsic brain and spine morphology in relation to function have developed over the past 30 years. Amongst these imaging modalities, functional magnetic resonance imaging (fMRI) is of particular interest since it follows the physiological coupling between neuronal electrical activity and metabolic structural (cellular) activity as it relates to tissue vascularity and perfusion states. This structure–function synesis (from the Greek noun, σύνεσις = being together), leads to three effects that contribute to the fMRI signal: an increase in the blood flow velocity, a change in the mean blood volume, and most importantly, alterations in the blood oxygenation level. The latter effect has lent to the development of blood-oxygenation-level-dependent or BOLD fMRI, which has been used in establishing the topographic relationship between eloquent cortex and neurosurgical planning. As an adjunct to this modality, MRI-based diffusion tensor imaging (DTI) allows further detailed radiographic assessment of fiber tracts in the brain in relationship to the surgical lesion of interest. Herein we review the roles of fMRI and DTI for presurgical mapping to allow for maximal safe resection procedures in neurosurgery with case-based illustrations

Cranio-spinal migration of a metallic clip placed during arteriovenous malformation resection - A case report, review of the literature, and management strategies

<p>Abstract</p> <p>Background</p> <p>Microclip placement during AVM resection is generally accepted to be a safe practice in neurosurgery. Here, we describe an unusual complication involving cranio-spinal clip migration discovered five years after the initial AVM surgery.</p> <p>Case Presentation</p> <p>A 53-year-old man underwent resection of a superior vermian AVM that required the placement of two microclips during the procedure. Five years after surgery, the patient suffered from descending sensory radiculopathy that resolved spontaneously. The workup revealed cranio-spinal migration of one of the previously placed microclips.</p> <p>Conclusions</p> <p>AVM clip migration is a rare phenomenon; however, the diagnosis should be entertained in patients with posterior fossa instrumentation who suffer from unusual neurologic symptoms.</p

Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1

Summary Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant autism linked to increased gene dosages of UBE3A, which both possesses ubiquitin-ligase and transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the nucleus down-regulates glutamatergic synapse organizer cerebellin-1 (Cbln1) that is needed for sociability in mice. Epileptic seizures also repress Cbln1 and are found to expose sociability impairments in mice with asymptomatic increases of UBE3A. This Ube3a-seizure synergy maps to glutamate neurons of the midbrain ventral tegmental area (VTA) where Cbln1 deletions impair sociability and weaken glutamatergic transmission. We provide preclinical evidence that viral-vector-based chemogenetic activations of, or Cbln1 restorations in VTA glutamatergic neurons rescues sociability deficits induced by Ube3a and/or seizures. Our results suggest a gene × seizure interaction in VTA glutamatergic neurons that impairs sociability by downregulating Cbln1, a key node in the expanding protein interaction network of autism genes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Maturation of projection neurons in the visual cortex of the rat

A variety of in vitro brain slice preparations were employed to study the development of electrophysiological and morphological characteristics of pyramidal neurons from layer 5 of the rat visual cortex. By combining conventional intracellular recording techniques with intracellular dye injection into neurons which were back-labelled from their respective target, it was possible to demonstrate a correlation between the intrinsic electrophysiological properties and the morphology of projection neurons. Superior colliculus projecting neurons fired action potentials in a burst-firing pattern whereas interhemispheric projecting neurons fired action potentials in a regular spiking pattern. Both groups differed also in the morphology of their dendritic arborizations. A developmental study of the physiological properties of morphologically identified layer 5 neurons demonstrated that subthreshold properties and characteristic action potential parameters of these neurons change progressively during the early postnatal period. Membrane time constants and input resistances changed to lower values and action potentials became higher, faster and thus briefer. No burst-firing patterns were found in early developmental stages. Using intracellular injection of Lucifer Yellow in fixed slices, it was then shown that superior colliculus (SC) projecting neurons and interhemispheric (CLH) projecting neurons differ significantly in their morphology already early in development. SC-nneurons have more basal dendrites which give rise to more branches and total tips than neurons projecting to the CLH.</p