Case 325: Persistent Craniopharyngeal Canal.

HISTORY: A 76-year-old female patient with a history of rheumatoid arthritis, Sjögren syndrome, and hypertension presented with headache, fever, and dysphagia. The patient was taking prednisone and leflunomide to treat rheumatoid arthritis. The headache was primarily left sided and occasionally radiated to the occipital region. The patient had a high-grade fever spike, with a temperature of 104 °F (40 °C). Results of a prior lumbar puncture and temporal artery biopsy from an outside hospital were negative. Findings of a neurologic examination were unremarkable. Oropharyngeal examination for dysphagia revealed minimal pharyngeal motility, with pooling of food in the pharynx, which was thought to be due to cranial nerve dysfunction. Laboratory analysis revealed that, except for anemia, complete blood count parameters were within normal limits. C-reactive protein level (49.7 mg/L; reference range, 0.0-8.0 mg/L), erythrocyte sedimentation rate (>140 mm/h with Westergren method; reference range, 0-27 mm/h), and brain-type natriuretic peptide level (145 pg/mL; reference range, 0-100 pg/mL) were elevated. Blood and urine cultures were negative. A lumbar puncture was performed, which revealed cloudy cerebrospinal fluid (CSF), with an elevated CSF protein level (78 mg/dL; reference range, 7.0-35.0 mg/dL) and a low CSF glucose level (37 mg/dL [2.05 mmol/L]; reference range, 45-70 mg/dL [2.50-3.89 mmol/L]); otherwise, CSF encephalopathy, an autoimmune panel, and cultures were negative. CT and MRI of the brain with paranasal sinus were performed. Nasal endoscopy-guided drainage of the preclival fluid collection was performed, and biopsy of nasopharyngeal tissue was performed. Fluid culture revealed the growth of Candida albicans, as well as Pseudomonas and Enterobacter aerogenes. The patient received fluconazole, ceftriaxone, vancomycin, and metronidazole. Follow-up MRI was performed after 2 weeks.

Case 325.

HISTORY: A 76-year-old woman with a history of rheumatoid arthritis, Sjögren syndrome, and hypertension presented with a headache, fever, and dysphagia. The patient was taking prednisone and leflunomide to treat rheumatoid arthritis. Her headache was primarily left sided and occasionally radiated to the occipital region. The patient had a high-grade fever spike, with a temperature of 104°F (40°C). Results of a prior lumbar puncture and temporal artery biopsy from an outside hospital were negative. Findings of a neurologic examination were unremarkable. Oropharyngeal examination for dysphagia revealed minimal pharyngeal motility, with pooling of food in the pharynx, which was thought to be due to cranial nerve dysfunction. Laboratory analysis revealed that, except for anemia, complete blood count parameters were within normal limits. C-reactive protein level (49.7 mg/L; reference range, 0.0-8.0 mg/L), erythrocyte sedimentation rate (>140 mm/h with Westergren method; reference range, 0-27 mm/h), and brain-type natriuretic peptide level (145 pg/mL; reference range, 0-100 pg/mL) were elevated. Blood and urine cultures were negative. A lumbar puncture was performed, which revealed cloudy cerebrospinal fluid (CSF), with an elevated CSF protein level (78 mg/dL; reference range, 7.0-35.0 mg/dL) and a low CSF glucose level (37 mg/dL [2.05 mmol/L]; reference range, 45-70 mg/dL [2.50-3.89 mmol/L]); otherwise, CSF encephalopathy, an autoimmune panel, and cultures were negative. MRI and CT scans of the brain with paranasal sinus were performed (Figs 1-3). Nasal endoscopy-guided drainage of the preclival fluid collection was performed, and biopsy of nasopharyngeal tissue was performed. Fluid culture revealed the growth of Candida albicans, as well as Pseudomonas and Enterobacter aerogenes. The patient received fluconazole, ceftriaxone, vancomycin, and metronidazole. Follow-up MRI was performed after 2 weeks (Fig 4).

Robot-Assisted Thoracolumbar Fixation After Acute Spinal Trauma: A Case Series.

BACKGROUND: Pedicle screw fixation has become the workhorse for the stabilization of the thoracolumbar spine. Since accurate pedicle screw placement is necessary for a successful surgery, three-dimensional navigation has become a mainstay for placing pedicle screws. However, the published studies have an overrepresentation of lumbar screws despite the prevalence of thoracic fractures. Furthermore, no robotic-assisted pedicle screw study has focused solely on traumatic fractures. The goal of this study was to address whether (1) robot-assisted pedicle screw placement had comparable accuracy in the thoracic and thoracolumbar region and (2) robot-assisted spine surgery was feasible in an acute, traumatic setting. METHODS: We performed 14 consecutive, thoracolumbar spinal stabilization procedures in which 126 pedicle screws were placed using the Globus ExcelsiusGPS® spine robot in an acute, traumatic setting. Operative times were measured, and the accuracy of pedicle screws was assessed with the Gertzbein and Robbins classification system by two board-certified neuroradiologists. RESULTS: A total of 60-thoracic (T3-T11), the 24-thoracolumbar junction (T12-L1), 40-lumbar (L2-L5), and two-sacral pedicle screws were placed. Pedicle screw placement was accurate with a < 1% (1/126) pedicle breach rate. Thoracolumbar robotic spine surgery in an acute, traumatic setting was demonstrated to have a good safety profile with only one minor neurological deficit which was related to positioning. Furthermore, surgical times were inversely related to the case number. CONCLUSIONS: These results together suggest that robot-assisted spine surgery is accurate in the thoracic spine. Furthermore, placement of thoracolumbar screws in an acute trauma is non-inferior to other methods when based on accuracy.

Torcular pseudomass in a 14-month-old child: illustrative case.

BACKGROUND: "Torcular pseudomass," or redundant soft tissue in the torcular region, is not an infrequent incidental finding on advanced imaging of the brain in infants and young children. It was recently codified among pediatric neuroradiologists; however, its report in the pediatric neurosurgical community has not previously been elucidated. OBSERVATIONS: The authors present a case of a 14-month-old child who presented with fever and a first-time seizure. Computed tomography of the head suggested an epidural abscess; however, magnetic resonance imaging characteristics of the lesion were consistent with torcular pseudomass, a normal variant. At the 3-month follow-up, the child was continuing to do well and had not had another seizure. There have been no indications for surgical intervention or additional radiographic surveillance. LESSONS: The differential diagnosis for torcular pseudomass includes dural venous sinus thrombosis, dermoid cysts, occipital encephalocele, eosinophilic granuloma, and primary and metastatic tumors, such as neuroblastoma. The management of each of these disorders in the differential diagnosis may be much more invasive than continued observation in the case of torcular pseudomass. Therefore, it is important for pediatric neurosurgeons to become familiar with this developmental anomaly of the dura and occipital skull.

Assessment of Mutation Drift Equilibrium and the Occurrence of a Recent Genetic Bottleneck in South Indian Zebu Cattle.

During the last few decades, the effective population size of indigenous zebu cattle breeds has declined drastically, resulting in the classification of some of them into the vulnerable, endangered, or critically endangered category. Drastic reductions in the effective size of a population may result in genetic bottlenecks and can affect within-breed genetic variability and its viability. The present study was undertaken with the objective of evaluating South Indian zebu cattle populations for mutation drift equilibrium and to detect the occurrence of recent genetic bottleneck events. A total of 293 cattle from eight indigenous breeds were genotyped at 27 FAO/ISAG-recommended microsatellite marker loci. Three different statistical tests, viz., the sign test, standardized differences test, and Wilcoxon sign rank test were performed using allele frequency data to detect loci with heterozygosity excess under the infinite alleles, stepwise, and two-phase mutation models. Under the infinite alleles model, the observed number of loci with heterozygosity excess (He > Heq) ranged between 10 and 19 among the investigated cattle breeds. However, the observed heterozygosity excess was not statistically significant (p > 0.05) in any of the studied breeds. Similarly, the standardized differences test and Wilcoxon sign rank test revealed no concrete evidence for the occurrence of a recent genetic bottleneck in South Indian zebu cattle breeds. The qualitative test for mode-shift distortion revealed a normal L-shaped distribution of allele frequencies, suggesting a lack of evidence for the loss of low-frequency alleles in all the investigated South Indian zebu cattle breeds.

Single nucleotide polymorphism in STAT5A could not endorse variation in milk production traits in Indian bovine population.

The Signal Transducer and Activator of Transcription 5A (STAT5A) gene involved in activating the transcription of milk protein genes was predicted to be influencing milk production traits. The present study was undertaken to investigate the suitability of the polymorphism of STAT5A as a marker for milk traits in Ongole, crossbred cattle and Murrah buffaloes from Southern India. Blood samples (n = 502) for DNA isolation and milk samples (n = 222) from different genetic groups were collected from various farms. The gene variants upon polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on the exon 7 region of STAT5A were subjected to GLM analysis to evaluate their association with milk production traits. The frequencies of C and T alleles at the STAT5A/AvaI locus were 0.98 and 0.02 (Jersey crossbred), 0.94 and 0.06 [Holstein-Friesian (HF) crossbred], 0.97 and 0.03 (Ongole). T allele was not observed in Murrah buffaloes. The least squares mean lactation milk yield of CC and CT genotypes of STAT5A were 2,096.90 ± 48.63 and 2,294.41 ± 215.85 kg in Jersey crossbred, 2,312.92 ± 91.01 and 2,392.82 ± 207.66 kg in HF crossbred and 528.40 ± 22.10 and 396.37 ± 76.17 kg in Ongole cattle, respectively. The milk fat content of the CC genotype was higher (P > 0.05) in Jersey crossbred cattle. The CT genotypes of Ongole and HF crossbred cattle recorded a higher fat per cent than the CC genotypes. Significant associations were not observed in support of STAT5A as a marker for milk production traits in either Ongole or crossbred cattle of indicine admixture and no reason could be found to consider this locus as universal markers for milk production traits in indicine cattle and buffaloes. Considering the monomorphic nature of the gene in buffaloes and their higher milk fat content as compared to bovine milk, much remains to be explored regarding the underlying differences across the bovine and the bubaline species.

MR Imaging of the Fetal Face: Comprehensive Review.

The human face is a complex anatomic structure with an equally complex embryologic development. Derangement of the developmental process can result in various structural anomalies, which range from a mainly cosmetic deformity, such as cleft lip, to potentially life-threatening conditions such as arhinia. These anomalies (a) can occur as isolated anomalies; (b) can be associated with intracranial, spinal, or dental anomalies; or (c) can be a part of various syndromes, thus serving as diagnostic clues in such cases. Proper evaluation of fetal facial deformities can help in prognostication, family counseling, and prenatal or early postnatal intervention. Ultrasonography (US) is the first line of investigation in these cases. However, when US does not allow complete evaluation of these anomalies owing to its inherent limitations, magnetic resonance (MR) imaging allows comprehensive evaluation of the anomaly itself and also evaluation of various associations and the treatment approach. The embryology of the fetal facial structures is considered with regard to the MR imaging technique and the MR imaging anatomy. The MR imaging features of various structural anomalies are described and classified into six groups, namely, orofacial clefts, orbital anomalies, nasal anomalies, facial masses, external ear anomalies, and abnormal face shape or profile. Also, the key associations and relevant treatment implications are reviewed. The article provides a "one-stop shop" review of these unique disorders-from basic understanding of the embryology to applying the knowledge in clinical practice, helping the interprofessional team and the patients alike. ©RSNA, 2018.

Looped back fiber mode for reduction of false alarm in leak detection using distributed optical fiber sensor.

Optical-fiber-based sensors have inherent advantages, such as immunity to electromagnetic interference, compared to the conventional sensors. Distributed optical fiber sensor (DOFS) systems, such as Raman and Brillouin distributed temperature sensors are used for leak detection. The inherent noise of fiber-based systems leads to occasional false alarms. In this paper, a methodology is proposed to overcome this. This uses a looped back fiber mode in DOFS and voting logic is employed to considerably reduce the false alarm rate.

Nuclear factor-kappaB mediates the inhibitory effects of tumor necrosis factor-alpha on growth hormone-inducible gene expression in liver.

TNF inhibits serine protease inhibitor 2.1 (Spi 2.1) and IGF-I gene expression by GH in CWSV-1 hepatocytes. The current study describes construction of a GH-inducible IGF-I promoter construct and investigates mechanisms by which TNF and nuclear factor-kappaB (NFkappaB) inhibit GH-inducible gene expression. CWSV-1 cells were transfected with GH-inducible Spi 2.1 or IGF-I promoter luciferase constructs, incubated with TNF signaling inhibitors (fumonisin B1 for sphingomyelinase and SP600125 for c-Jun N-terminal kinase), treated with or without TNF, and then stimulated with recombinant human GH. The 5- to 6-fold induction of Spi 2.1 and IGF-I promoter activity by GH was inhibited by TNF. Neither fumonisin B1 nor SP600125 prevented the inhibitory effects of TNF on GH-inducible promoter activity. Dominant-negative inhibitor-kappaBalpha (IkappaBalpha) expression vectors (IkappaBalphaS/A or IkappaBalphaTrunc), p65 and p50 expression vectors, and p65 deletion constructs were used to investigate the NFkappaB pathway. IkappaBalphaS/A and IkappaBalphaTrunc ameliorated the inhibitory effects of TNF on GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection of CWSV-1 cells with expression vectors for p65 alone or p50 and p65 together inhibited GH-inducible Spi 2.1 and IGF-I promoter activity. Cotransfection with a C-terminal p65 deletion (1-450) enhanced GH-inducible promoter activity, whereas the N-terminal deletion (31-551) was inhibitory for IGF-I but not Spi 2.1. Cycloheximide did not antagonize the inhibitory effects of TNF on GH-inducible IGF-I expression. We conclude the inhibitory effects of TNF on GH-inducible promoter activity are mediated by NFkappaB, especially p65, by a mechanism that does not require protein synthesis.

Nuclear factor kappaB mediates the inhibitory effects of interleukin-1 on growth hormone-inducible gene expression.

BACKGROUND: Hepatic expression of growth hormone (GH)-inducible genes serine protease inhibitor (Spi 2.1) and insulin-like growth factor (IGF)-I are inhibited by interleukin (IL)-1. The current study examines the role of the nuclear factor kappaB (NFkappaB) pathway and suppressor of cytokine signaling (SOCS)-3 expression as potential mechanisms for IL-1-mediated GH resistance. METHODS: CWSV-1 hepatocytes were cotransfected with Spi 2.1 or IGF-1 promoter luciferase constructs and empty pCMV4 vector or dominant negative inhibitor-kappaBalpha (IkappaBalpha)S/A construct. Cells were treated with or without IL-1 and then stimulated with or without recombinant human GH. Cell extracts were assayed for luciferase activity and protein, normalized and expressed as fold-induction. CWSV-1 cells transfected with pCMV4 or IkappaBalphaS/A were treated with or without IL-1 then SOCS-3 mRNA was measured. Finally, CWSV-1 cells were cotransfected with a SOCS-3 promoter construct with or without pCMV4 or IkappaBalphaS/A and then stimulated with or without IL-1 to investigate SOCS-3 promoter activity. RESULTS: CWSV-1 cells cotransfected with pCMV4 demonstrated a three- to fivefold induction of Spi 2.1 or IGF-1 promoter activity after GH stimulation that was almost completely inhibited by IL-1. Cotransfection with IkappaBalphaS/A increased GH-inducible Spi 2.1 and IGF-1 promoter activity, but the inhibitory effects of IL-1 on both promoters were attenuated by cotransfection with IkappaBalphaS/A. IL-1 stimulated SOCS-3 mRNA expression and promoter activity. Cotransfection with IkappaBalphaS/A increased IL-1-inducible SOCS-3 promoter activity, but not SOCS-3 mRNA or protein. CONCLUSIONS: Signaling via the NFkappaB pathway is responsible for the inhibitory effects of IL-1 on GH-inducible gene expression by a mechanism that does not seem to involve increased SOCS-3 expression.

Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes.

During systemic inflammation, the liver becomes unresponsive to growth hormone (GH), resulting in decreased plasma insulin-like growth factor-I (IGF-I) with concomitant reductions in lean body mass. Transgenic mice that overexpress IL-6 also demonstrate impaired growth and decreased IGF-I. To determine whether IL-6 directly inhibits GH-inducible gene expression, CWSV-1 hepatocytes were incubated with IL-6 (10 ng/ml), then stimulated with recombinant human GH (500 ng/ml, 18 h). The increase in IGF-I and serine protease inhibitor 2.1 (Spi 2.1) mRNA in GH-treated cells was inhibited by treatment with IL-6 for 24 h. To investigate potential mechanisms, we examined the effects of IL-6 on GH receptor (GHR) expression and GH signaling via the JAK/signal transducer and activator of transcription (STAT) and MAP kinase pathways. Incubation of cells with IL-6 (10 ng/ml, 24 h) had no effect on GHR abundance or signaling proteins JAK2, STAT5b, and ERK1/2. Although GH transiently increased (2- to 5-fold) the tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2, IL-6 did not alter these phosphorylation events. However, nuclear protein from IL-6-treated cells demonstrated reduced STAT5 DNA binding (by EMSA) at 15 min (-20%) and 60 min (-43%) after GH stimulation. To determine whether IL-6 inhibits GH-inducible promoter activity, CWSV-1 cells were transfected with Spi 2.1 or prolactin receptor promoter luciferase vectors, incubated with or without IL-6, then stimulated with GH. The induction of both Spi 2.1 (7.5-fold) and prolactin receptor (4-fold) promoter activity by GH was inhibited by IL-6. In summary, IL-6 mediates hepatic GH resistance by a time-dependent inhibition of GH-inducible promoter activity that is associated with reductions in STAT5 DNA binding.

Ceramide recruits and activates protein kinase C zeta (PKC zeta) within structured membrane microdomains.

We have previously demonstrated that hexanoyl-D-erythro-sphingosine (C(6)-ceramide), an anti-mitogenic cell-permeable lipid metabolite, limited vascular smooth muscle growth by abrogating trauma-induced Akt activity in a stretch injury model of neointimal hyperplasia. Furthermore, ceramide selectively and directly activated protein kinase C zeta (PKC zeta) to suppress Akt-dependent mitogenesis. To further analyze the interaction between ceramide and PKC zeta, the ability of ceramide to localize within highly structured lipid microdomains (rafts) and activate PKC zeta was investigated. Using rat aorta vascular smooth muscle cells (A7r5), we now demonstrate that C(6)-ceramide treatment results in an increased localization and phosphorylation of PKC zeta within caveolin-enriched lipid microdomians to inactivate Akt. In addition, ceramide specifically reduced the association of PKC zeta with 14-3-3, a scaffold protein localized to less structured regions within membranes. Pharmacological disruption of highly structured lipid microdomains resulted in abrogation of ceramide-activated, PKC zeta-dependent Akt inactivation, whereas molecular strategies suggest that ceramide-dependent PKC zeta phosphorylation of Akt3 at Ser(34) was necessary for ceramide-induced vascular smooth muscle cell growth arrest. Taken together, these data demonstrate that structured membrane microdomains are necessary for ceramide-induced activation of PKC zeta and resultant diminished Akt activity, leading to vascular smooth muscle cell growth arrest.

Exercise training differentially modifies age-associated alteration in expression of Na+-K+-ATPase subunit isoforms in rat skeletal muscles.

The present study tests the hypothesis that endurance exercise training (ETr) reverses age-associated alterations in expression of Na+-K+-ATPase subunit isoforms in rat skeletal muscles. Expression of the isoforms was examined in 16-mo-old sedentary middle-aged, 29-mo-old sedentary senescent, and 29-mo-old treadmill exercise-trained senescent Fischer 344 x Brown Norway rats. Levels of the alpha1-isoform increased with age in red gastrocnemius (GR), white gastrocnemius (GW), and extensor digitorum longus (EDL) muscles, and ETr further increased its levels. Levels of the alpha2-isoform were unchanged in GR, had a strong trend for a decrease in GW, and decreased significantly in EDL. ETr increased expression of the alpha2-isoform in all three muscle groups. There was no increase in expression of the beta1-isoform in GR, GW, or EDL with age, whereas ETr markedly increased its levels in the muscles. There was a marked decrease with age in expression of the beta2-isoform in the muscle groups that was not reversed by ETr. By contrast, beta3-isoform levels increased with age in GR and GW, and ETr was able to reverse this increase. Na+-K+-ATPase enzyme activity was unchanged with age in GR and GW but increased in EDL. ETr increased enzyme activity in GR and GW and did not change in EDL. Myosin heavy chain isoforms in the muscle groups did not change significantly with age; ETr caused a general shift toward more oxidative fibers. Thus ETr differentially modifies age-associated alterations in expression of Na+-K+-ATPase subunit isoforms, and a mechanism(s) other than physical inactivity appears to play significant role in some of the age-associated changes.