Sinking skin flap syndrome in a patient with bone resorption after cranioplasty and ventriculoperitoneal shunt placement: illustrative case.

BACKGROUND: Sinking skin flap syndrome (SSFS) is an uncommon complication that can follow decompressive craniectomy. Even less common is the development of SSFS following bone resorption after cranioplasty with exacerbation by a ventriculoperitoneal (VP) shunt. OBSERVATIONS: A 56-year-old male sustained a severe traumatic brain injury and subsequently underwent an emergent decompressive craniectomy. After craniectomy, a cranioplasty was performed, and a VP shunt was placed. The patient returned to the emergency department 5 years later with left-sided hemiplegia and seizures. His clinical presentation was attributed to complete bone flap resorption (BFR) complicated by SSFS likely exacerbated by his VP shunt and the resultant mass effect on the underlying brain parenchyma. The patient underwent surgical intervention via synthetic bone flap replacement. Within 6 days, he recovered to his baseline neurological status. LESSONS: SSFS after complete BFR is a rare complication following cranioplasty. To the authors' knowledge, having a VP shunt in situ to exacerbate the clinical picture has yet to be reported in the literature. In addition to presenting the case, the authors also describe an effective treatment strategy of decompressing the brain and elevating the scalp flap while addressing the redundant tissue, then using a synthetic mesh to reconstruct the calvarial defect while keeping the shunt in situ.

Obtuse-angled Laminotomy as a Modification of Multilevel Laminectomy for Spinal Cord Decompression.

The purpose of this note is to describe an obtuse-angled laminotomy of C7 during cervical decompression that aims to preserve cervicothoracic junction stability and potentially reduce pain. Cervical spondylotic myelopathy can result from degenerative cervical spinal disease including, herniated disk material, osteophytes, redundant ligamentum flavum, or ossification of the posterior longitudinal ligament. Surgical intervention for multilevel myelopathy aims to decompress the spinal cord and maintain stability of the cervical spine. Multilevel laminectomy is traditionally used when degenerative changes affect 3 or more levels and when there is primarily dorsal compressive disease. Traditional laminectomy can result in instability and kyphosis. The C7 lamina can be particularly vulnerable given the location at cervicothoracic junction. We describe an obtuse-angled laminotomy for the most caudal lamina in a planned decompression. This lamina is left attached to ligamentum nuchea, adjacent fascia, and paravertebral muscles. Only the base of spinous process and ventral portion of lamina's cortical and cancellous bone are removed in an obtuse angle through the opening. This variation is aimed to preserve as much of the cervical stability while still achieving the goal of decompression.

Interaction and antagonistic roles of NF-κB and Hes6 in the regulation of cortical neurogenesis.

The involvement of nuclear factor kappa B (NF-κB) in several processes in the postnatal and adult brain, ranging from neuronal survival to synaptogenesis and plasticity, has been documented. In contrast, little is known about the functions of NF-κB during embryonic brain development. It is shown here that NF-κB is selectively activated in neocortical neural progenitor cells in the developing mouse telencephalon. Blockade of NF-κB activity leads to premature cortical neuronal differentiation and depletion of the progenitor cell pool. Conversely, NF-κB activation causes decreased cortical neurogenesis and expansion of the progenitor cell compartment. These effects are antagonized by the proneuronal transcription factor Hes6, which physically and functionally interacts with RelA-containing NF-κB complexes in cortical progenitor cells. In turn, NF-κB exerts an inhibitory effect on the ability of Hes6 to promote cortical neuronal differentiation. These results reveal previously uncharacterized functions and modes of regulation for NF-κB and Hes6 during cortical neurogenesis.

Intrathecal catheter-tip inflammatory masses: an intraparenchymal granuloma.

The authors report the case of a 54-year-old woman who presented with an intraparenchymal granuloma in her lower thoracic spinal cord. On imaging studies there was an intramedullary enhancement at the left dorsal aspect of the cord immediately adjacent to the tip of an intrathecal arachnoid catheter used for intraspinal drug therapy. At surgery, it was apparent that once this superficial component of the catheter and inflammatory mass was removed, there was a granulomatous component that extended into the spinal cord. A 5-mm caseating chalklike granuloma was carefully dissected away. To the authors' knowledge, this is the first reported case of an intrathecal catheter-tip granuloma growing inside the spinal cord parenchyma.

Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation.

Hairy/Enhancer of split (Hes) 6 is a basic helix-loop-helix protein that interacts with the transcriptional co-repressor, Groucho, and antagonizes the neural functions of the Notch pathway. More specifically, mouse Hes6 regulates cerebral corticogenesis by promoting neurogenesis and suppressing astrocyte differentiation. The molecular mechanisms underlying the anti-astrogenic function of Hes6 are poorly defined. Here we describe studies aimed at testing whether Hes6 inhibits astrocyte differentiation by antagonizing the transcription repression activity of Notch-activated Hes family members like Hes1. It is reported that Hes6 preferentially forms homodimers. Heterodimerization with Hes1 is antagonized in part by a conserved N-terminal patch of negatively charged residues. Mutation of this motif enhances heterodimerization with Hes1 and increases Hes6 ability to antagonize Hes1-mediated transcriptional repression. However, this mutation does not increase, but instead decreases, the anti-astrogenic activity of Hes6. It is shown further that Hes6 harbors a second conserved sequence, a C-terminal SPXXSP motif. This sequence is phosphorylated by the mitogen activated protein kinase pathway and its mutation disrupts the anti-astrogenic activity of Hes6 without affecting its ability to suppress Hes1. Together, these observations suggest that Hes6 homodimers regulate astrocyte differentiation through mechanisms that depend on the phosphorylation of Hes6 C-terminal domain but are independent of its ability to suppress Hes1-mediated transcriptional repression.

Hes6 inhibits astrocyte differentiation and promotes neurogenesis through different mechanisms.

The mechanisms regulating the generation of cell diversity in the mammalian cerebral cortex are beginning to be elucidated. In that regard, Hairy/Enhancer of split (Hes) 1 and 5 are basic helix-loop-helix (bHLH) factors that inhibit the differentiation of pluripotent cortical progenitors into neurons. In contrast, a related Hes family member termed Hes6 promotes neurogenesis. It is shown here that knockdown of endogenous Hes6 causes supernumerary cortical progenitors to differentiate into cells that exhibit an astrocytic morphology and express the astrocyte marker protein GFAP. Conversely, exogenous Hes6 expression in cortical progenitors inhibits astrocyte differentiation. The negative effect of Hes6 on astrocyte differentiation is independent of its ability to promote neuronal differentiation. We also show that neither its proneuronal nor its anti-gliogenic functions appear to depend on Hes6 ability to bind to DNA via the basic arm of its bHLH domain. Both of these activities require Hes6 to be localized to nuclei, but only its anti-gliogenic function depends on two short peptides, LNHLL and WRPW, that are conserved in all Hes6 proteins. These findings suggest that Hes6 is an important regulator of the neurogenic phase of cortical development by promoting the neuronal fate while suppressing astrocyte differentiation. They suggest further that separate molecular mechanisms underlie the proneuronal and anti-gliogenic activities of Hes6 in cortical progenitor cells.