The Extended-Sphenoid Ridge Approach: A New Technique for the Surgical Treatment of Skull Base Tumors in Pediatric Patients.

The sphenoid ridge approach (SRA) was initially described as a surgical technique for treating vascular pathologies near the Sylvian fissure. However, limited studies have systematically explored the use of skull base techniques in pediatric patients. This study investigated an extended variation in the sphenoid ridge approach (E-SRA), which systematically removed the pterion, orbital walls (roof and lateral wall), greater sphenoid wing, and anterior clinoid process to access the base of the skull. OBJECTIVE: This report aimed to evaluate the advantages of the extradural removal of the orbital roof, pterion, sphenoid wing, and anterior clinoid process as a complement to the sphenoid ridge approach in pediatric patients. PATIENTS AND METHODS: We enrolled 36 patients with suspected neoplastic diseases in different regions. The E-SRA was performed to treat the patients. Patients were included based on the a priori objective of a biopsy or a total gross resection. The surgical time required to complete the approach, associated bleeding, and any complications were documented. RESULTS: Our results demonstrated that the proposed a priori surgical goal, biopsy, or resection were successfully achieved in all cases. In addition, using the E-SRA technique was associated with a shorter operative time, minimal bleeding, and a lower incidence of complications. The most frequently encountered complications were related to dural closure. CONCLUSIONS: The extended sphenoid ridge approach represents a safe and effective option for managing intracranial tumors in pediatrics.

Perceptions of quality of communication in family interactions in neurocritical care.

OBJECTIVE: Given the challenges of patient-provider communication in neurocritical care lacking robust decision-making tools on prognostication, we investigated concordance in perceptions of communication among participants in family discussions and assess the different domains of communication that affect these perceptions. METHODS: Prospective observational study conducted over 4 months in a tertiary-level academic medical center neurocritical care unit. Our study involved family discussions regarding plan of care for admitted patients observed by a neutral observer. All participants completed a survey. The first four questions rated the understanding of the discussion and general satisfaction; the remaining questions were open-ended to assess the quality of communication by the physician leading the discussion. Responses were scored and compared among participants using a Likert scale. A difference of < 1 in scores among participants was rated as concordance, whereas that of > 1 was designated as discordance. All open-ended responses were classified into six domains. RESULTS: We observed 35 family discussions. Questions 1 to 3 inquiring on general satisfaction, impact, and understanding of treatment options yielded 99 cross-comparisons per question (297 compared responses). Most responses were either "Strongly Agree" or "Agree," with "Neutral" or "Disagree" responses being more prevalent in Question 2 regarding the impact of the conversation. Overall concordance of responses between participants was 88% with a lower rate of concordance (72%) on Q2. Further open-ended questions queried observers on specific physician-spoken content, and answers were analyzed to identify domains that affected the perception of quality of communication. Education was the most frequently cited domain of communication in response to open-ended questions. Among family and neutral observers, empathy was frequently listed, whereas providers more often listed family engagement. CONCLUSION: Overall, satisfaction was high among providers, families, and the observer regarding the quality of communication during family discussions in the unit. Perceptual differences emerged over whether this communication impacted healthcare decision-making during that encounter.

Nationwide Procedural Trends for Renal Trauma Management.

OBJECTIVE: To characterize national trends in procedural management of renal trauma. BACKGROUND: Management of renal trauma has evolved to favor a more conservative approach. For patients requiring intervention, there is a paucity of information to characterize the nature of procedural therapy administered. METHODS: A retrospective cross-sectional analysis was performed using data contained within the National Trauma Data Bank. The National Trauma Data Bank is a voluntary data repository managed by the American College of Surgeons, containing data regarding trauma admissions at 747 level I to V trauma centers throughout the United States and Canada. Participants included any patient with renal trauma requiring intervention from 2002 to 2012. They were identified according to International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes, with codes 866.00 through 866.03 for blunt renal trauma, and codes 866.10 through 866.13 for penetrating trauma. Cases were separated into those requiring nephrectomy, renorrhaphy, or endovascular repair based on ICD-9 procedure code. The number of cases performed each year and yearly trends as measured by linear regression. RESULTS: A total of 4296 cases were reported during the study period. Of these cases, 2635 involved blunt trauma and 1661 involved penetrating injury. There was a significant increase in the percentage of cases managed by endovascular means for both blunt and penetrating trauma (R = 0.92, P < 0.01; and R = 0.86, P < 0.01, respectively). This was primarily at the expense of nephrectomy, with cases showing significant decline in both groups. CONCLUSIONS: National trends for procedural management of renal trauma are toward less invasive interventions. These trends suggest favorable change towards renal preservation and decreased morbidity, potentially facilitated, in part, by improved radiographic staging and endovascular techniques, and also increased provider awareness of the safety and value of conservative management.

Failure of the inflatable penile prosthesis due to abnormal folding of a low-profile reservoir - A selected case from an overall series and systematic review.

We present a case from a running series of inflatable penile prosthesis failure due to improper folding of the Conceal™ reservoir. The Conceal™ Low-Profile reservoir gained popularity due to claims of improved cosmesis and ease of implantation. As the number of patients receiving this and other low-profile reservoirs increases, it is imperative to review and document any novel complications. While the Conceal™ reservoir may be preferred in ectopic placement, it may be more prone to fluid lockout facilitated by conformational change. Our review did not identify prior reports of improper folding, which we believe is unique to these low-profile reservoirs.

Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis.

Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 oncospheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments.

Antioxidant therapy reduces oxidative and inflammatory tissue damage in patients subjected to cardiac surgery with extracorporeal circulation.

Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.

Hepatocyte growth factor in cerebrospinal fluid is associated with mortality and recurrence of glioblastoma, and could be of prognostic value.

Malignant gliomas--glioblastoma multiforme and anaplastic astrocytoma--are among the most fatal forms of cancer in humans. It has been suggested that hepatocyte growth factor (HGF) is a reliable predictor of glioma malignancy; amounts of HGF are directly related to cellular proliferation, angiogenesis, low apoptotic rate, and poor prognosis (WHO III and IV). We measured the HGF content of cerebrospinal fluid (CSF) from patients with malignant glioma glioblastoma multiforme (WHO IV; n = 14), anaplastic astrocytoma (WHO III; n = 4), and meningioma (WHO I; n = 9), and from control subjects (n = 25), and found a high concentration of HGF in patients with malignant glioma. However, CSF concentrations from glioblastoma multiforme and anaplastic astrocytoma patients were not statistically significantly different (893 +/- 157 vs. 728 +/- 61, respectively; P > 0.01). A negative correlation between HGF and survival was found at five years of follow-up (R = -0.922, R (2) = 0.850, P < 0.001). Also, the HGF concentration in CSF was a reliable means of explaining the highly variable survival of patients with malignant glioma. CSF concentrations of HGF higher than 500 pg/ml were associated with increased mortality whereas values higher than 850 pg/ml were associated with a brief tumor-free period after surgery (9 +/- 0.6 vs. 6 +/- 0.6 months, respectively, P < 0.001). Our findings support the idea that measurement of HGF in CSF could be a useful tool for monitoring the biological activity of malignant glioma. The findings will ultimately need to be confirmed in a much larger study.

Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model.

Exploitation of the ability of stem cells to protect damaged neuronal tissue may be a more viable strategy than cell replacement for repair of the central nervous system (CNS). In this study we assessed the capacity of human umbilical cord blood (hUCB)-derived mesenchymal stromal cells (MSCs) to protect and promote regeneration of axotomised neurons within the rat optic system. The optic tract of neonatal rats was transected at the level of the lateral geniculate nucleus, and MSCs were introduced into the lesion site. MSCs survived well up to 2 weeks after grafting, and did not migrate significantly or differentiate. In the presence of MSC grafts, host axonal processes were found to be present in the lesion site, and there was stimulation of an endogenous neural precursor population. Four weeks after grafting, retrograde tracer experiments demonstrated that grafted MSCs, as well as cells of a human fibroblast line, exerted a neuroprotective effect, rescuing a significant percentage of axotomised retinal ganglion cells (RGCs). Further experiments with retrograde and anterograde tracers strongly indicated that MSCs could also promote re-growth of axotomised RGCs to their target, the superior colliculus (SC). Further analysis showed that hUCB-derived MSCs secreted several immunomodulatory and neurotrophic factors in vitro, including TGFbeta1, CNTF, NT-3 and BDNF, which are likely to play a role in neuroprotection. Our data indicate that hUCB-derived MSCs may be an easily accessible, widely available source of cells that can contribute towards neural repair through rescue and regeneration of injured neurons.

Rat neurosphere cells protect axotomized rat retinal ganglion cells and facilitate their regeneration.

We investigated the ability of a population of rat neural stem and precursor cells derived from rat embryonic spinal cord to protect injured neurons in the rat central nervous system (CNS). The neonatal rat optic pathway was used as a model of CNS injury, whereby retinal ganglion cells (RGCs) were axotomized by lesion of the lateral geniculate nucleus one day after birth. Neural stem and precursor cells derived from expanded neurospheres (NS) were transplanted into the lesion site at the time of injury. Application of Fast Blue tracer dye to the lesion site demonstrated that significant numbers of RGCs survived at 4 and 8 weeks in animals that received a transplant, with an average of 28% survival, though in some individual cases survival was greater than 50%. No RGCs survived in animals that received a lesion alone. Furthermore, labeled RGCs were also observed when Fast Blue was applied to the superior colliculus (SC) at 4 weeks, suggesting that neurosphere cells also facilitated RGC to regenerate to their normal target. Transplanted cells did not migrate or express neural markers after transplantation, and secreted several neurotrophic factors in vitro. We conclude that NS cells can protect injured CNS neurons and promote their regeneration. These effects are not attributable to cell replacement, and may be mediated via secretion of neurotrophic factors. Thus, neuroprotection by stem cell populations may be a more viable approach for treatment of CNS disorders than cell replacement therapy.

Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.

This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.

Analysis of neural potential of human umbilical cord blood-derived multipotent mesenchymal stem cells in response to a range of neurogenic stimuli.

We investigated the neurogenic potential of full-term human umbilical cord blood (hUCB)-derived multipotent mesenchymal stem cells (MSCs) in response to neural induction media or coculture with rat neural cells. Phenotypic and functional changes were assessed by immunocytochemistry, RT-PCR, and whole-cell patch-clamp recordings. Naive MSCs expressed both mesodermal and ectodermal markers prior to neural induction. Exposure to retinoic acid, basic fibroblast growth factor, or cyclic adenosine monophosphate (cAMP) did not stimulate neural morphology, whereas exposure to dibutyryl cAMP and 3-isobutyl-1-methylxanthine stimulated a neuron-like morphology but also appeared to be cytotoxic. All protocols stimulated increases in expression of the neural precursor marker nestin, but expression of mature neuronal or glial markers MAP2 and GFAP was not observed. Nestin expression increases were serum level dependent. Electrophysiological properties of MSCs were studied with whole-cell patch-clamp recordings. The MSCs possessed no ionic currents typical of neurons before or after neural induction protocols. Coculture of hUCB-derived MSCs and rat neural cells induced some MSCs to adopt an astrocyte-like morphology and express GFAP protein and mRNA. Our data suggest hUCB-derived MSCs do not transdifferentiate into mature functioning neurons in response to the above neurogenic protocols; however, coculture with rat neural cells led to a minority adopting an astrocyte-like phenotype.

Early alterations in the electrophysiological properties of rat spinal motoneurones following neonatal axotomy.

Early in development, motoneurones are critically dependent on their target muscles for survival and differentiation. Previous studies have shown that neonatal axotomy causes massive motoneurone death and abnormal function in the surviving motoneurones. We have investigated the electrophysiological and morphological properties of motoneurones innervating the flexor tibialis anterior (TA) muscle during the first week after a neonatal axotomy, at a time when the motoneurones would be either in the process of degeneration or attempting to reinnervate their target muscles. We found that a large number ( approximately 75%) of TA motoneurones died within 3 weeks after neonatal axotomy. Intracellular recordings revealed a marked increase in motoneurone excitability, as indicated by changes in passive and active membrane electrical properties. These changes were associated with a shift in the motoneurone firing pattern from a predominantly phasic pattern to a tonic pattern. Morphologically, the dendritic tree of the physiologically characterized axotomized cells was significantly reduced compared with age-matched normal motoneurones. These data demonstrate that motoneurone electrical properties are profoundly altered shortly after neonatal axotomy. In a subpopulation of the axotomized cells, abnormally high motoneurone excitability (input resistance significantly higher compared with control cells) was associated with a severe truncation of the dendritic arbor, suggesting that this excitability may represent an early electrophysiological correlate of motoneurone degeneration.

Lack of myostatin results in excessive muscle growth but impaired force generation.

The lack of myostatin promotes growth of skeletal muscle, and blockade of its activity has been proposed as a treatment for various muscle-wasting disorders. Here, we have examined two independent mouse lines that harbor mutations in the myostatin gene, constitutive null (Mstn(-/-)) and compact (Berlin High Line, BEH(c/c)). We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles. In addition, Mstn(-/-) muscle contracted and relaxed faster during a single twitch and had a marked increase in the number of type IIb fibers relative to wild-type controls. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle.

Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study.

The cytopathology and loss of neurons was studied in 7670 neurons from the ventral horn of the third lumbar segment of the spinal cord of six sporadic motor neuron disease (MND) patients compared with 7568 neurons in seven age matched control subjects. A modified Tomlinson et al. [Tomlinson BE, Irving D, Rebeiz JJ. Total numbers of limb motor neurones in the human lumbosacral cord and an analysis of the accuracy of various sampling procedures. J Neurol Sci 1973;20:313-27] sampling procedure was used for neuronal counts. The ventral horn was divided in quadrants. Neuronal populations were also classified by the maximum cell diameter through the nucleolus. There was widespread loss of neurons in all quadrants of the ventral horn in MND. Size distribution histograms showed similar neuron loss across all populations of neurons. The dorsomedial quadrant contains almost exclusively interneurons and the ventrolateral quadrant mostly motor neurons. The cytopathology of neurons in the dorsomedial quadrant and of large motorneurons in the ventrolateral quadrant MND was similar. In the dorsomedial quadrant, neuron loss (56.7%) was similar to the loss of large motor neurons in the ventrolateral quadrant (64.4%). The loss of presumed motor neurons and interneurons increased with increased disease duration. There was no evidence that loss of presumed interneurons occurred prior, or subsequent, to loss of motor neurons. We conclude that, in sporadic MND, all neuronal populations in the ventral horn are affected and that interneurons are involved to a similar extent and in parallel with motor neurons, as reported in the G86R transgenic mouse model of familial MND. The increasing evidence of loss of neurons other than motor neurons in MND suggests the need for revising the concept of selective motor neuron vulnerability.

Heat shock protein 27 rescues motor neurons following nerve injury and preserves muscle function.

Heat shock proteins (HSPs) are a family of ubiquitously expressed proteins that are up-regulated in response to a range of stresses and play an important role in cellular defence mechanisms. In previous studies, we demonstrated that overexpression of heat shock protein 27 (HSP27) in transgenic mice has significant cytoprotective properties in vivo, reducing caspase-3-mediated cell death in the hippocampus associated with limbic seizures and reducing infarct size in cardiac ischaemia. In motor neurons, HSP27 is also implicated as a survival promoting factor; however, it remains to be established whether HSP27 is able to exert long-term neuroprotective effects following neonatal nerve injury. We now show that, following neonatal nerve crush, HSP27 overexpression in vivo provides a substantial rescue of motor neurons 5-6 months following nerve injury. Furthermore, in vivo isometric tension recordings demonstrate that surviving motor neurons were able to regenerate, resulting in a 90% improvement (P < 0.0005) in motor unit number in HSP27 mice. Moreover, this increase in motor unit number was associated with improved muscle weight, muscle force, contractile speeds, and histochemical markers of muscle activity. These properties of HSP27 therefore have considerable potential for improving long-term muscle function in motor neuron disorders.

Brief presence of varicella-zoster vral DNA in mononuclear cells during relapses of multiple sclerosis.

BACKGROUND: A possible viral cause for multiple sclerosis (MS) has long been suspected. A progressive increase in MS has been reported in Mexico during the past 20 years; a conspicuous antecedent of varicella infection during childhood has been the most relevant finding in the medical history of patients with MS. OBJECTIVE: To investigate the possible participation of varicella-zoster virus (VZV) in the etiopathogenesis of MS. DESIGN, SETTING, AND PATIENTS: We searched, by polymerase chain reaction (PCR), for VZV DNA in peripheral mononuclear cells of 82 patients with relapsing-remitting MS. Additionally, genes gD from herpes simplex viruses 1 and 2 were sought by PCR, as well as IgG and IgM serum antibodies to VZV. RESULTS: Viral DNA from the genes open reading frame (ORF)31, ORF62, ORF63, and ORF67 of VZV was found in mononuclear cells from 13 (87%) of 15 patients with MS who were tested during acute relapse. All patients who were tested during remission (n = 67) were negative for the DNA, including patients who were initially positive and were tested again after 2 months of remission. All control patients with a comprehensive variety of neurologic diseases (n = 100) and healthy controls (n = 20) also tested negative. All subjects were negative for herpes simplex viruses 1 and 2 DNA, and no differences were found in serum antibodies to VZV. CONCLUSIONS: The finding of genes of VZV in peripheral mononuclear cells, restricted to a brief period during clinical relapse of MS, suggests either its participation in the etiopathogenesis of MS or an epiphenomenon of viral activation simultaneous with the relapse of MS.

Increased electrotonic coupling in spinal motoneurons after transient botulinum neurotoxin paralysis in the neonatal rat.

The effect of early postnatal blockade of neuromuscular transmission using botulinum neurotoxin (BoNT) type A on motoneuron gap junctional coupling was studied by means of intracellular recordings and biocytin labeling using the in vitro hemisected spinal cord preparation of neonatal rats. The somata of tibialis anterior (TA) motoneurons were retrogradely labeled at birth (P0) by intramuscular injection of fluorescent tracers. Two days later, BoNT was injected unilaterally into the TA muscle. The toxin blocked neuromuscular transmission for the period studied (P4-P7) as shown by tension recordings of the TA muscle. Retrograde horseradish peroxidase tracing in animals reared to adulthood demonstrated no significant cell death or changes in the soma size of BoNT-treated TA motoneurons. Intracellular recordings were carried out in prelabeled control and BoNT-treated TA motoneurons from P4 to P7. Graded stimulation of the ventral root at subthreshold intensities elicited short-latency depolarizing (SLD) potentials that consisted of several discrete components reflecting electrotonic coupling between two or more motoneurons. BoNT treatment produced a significant increase (67%) in the maximum amplitude of the SLD and in the number of SLD components as compared with control (3.1 +/- 1.7 vs. 1.4 +/- 0.7; means +/- SD). The morphological correlates of electrotonic coupling were investigated at the light microscope level by studying the transfer of biocytin to other motoneurons and the putative sites of gap junctional interaction. The dye-coupled neurons clustered around the injected cell with close somato-somatic, dendro-somatic and -dendritic appositions that might represent the sites of electrotonic coupling. The size of the motoneuron cluster was, on average, 2.2 times larger after BoNT treatment. Our findings demonstrate that a short-lasting functional disconnection of motoneurons from their target muscle delays motoneuron maturation by halting the elimination of gap junctional coupling that normally occurs during early postnatal development.