Frontonasal Encephalocele Complicated With Pseudotumor Cerebri: A Case Report and Literature Review.

Primary pseudotumor cerebri syndrome (PPTS) is a rare disorder of elevated intracranial pressure (ICP) in the absence of an identifiable underlying etiology. Afflicted patients are usually obese women in their reproductive age presenting with symptoms of elevated ICP. Seldom, patients can present with an encephalocele. We reported a case of a 31-year-old female who initially presented to our center with complaints of headaches, foreign body sensation in the nasal cavity, and decreased ability to smell. Brain computed tomography (CT) scan showed a large intranasal encephalocele and defect along the frontal skull base, through which brain tissue was herniating. The patient was successfully treated surgically by implantation of a lumboperitoneal shunt to manage the high ICP caused by her PPTS. In combination, reconstruction of the frontal skull base defect for the encephalocele was performed. Currently, the patient is doing well despite some on-and-off headaches.

Blockchain Integration With Digital Technology and the Future of Health Care Ecosystems: Systematic Review.

BACKGROUND: In the era of big data, artificial intelligence (AI), and the Internet of Things (IoT), digital data have become essential for our everyday functioning and in health care services. The sensitive nature of health care data presents several crucial issues such as privacy, security, interoperability, and reliability that must be addressed in any health care data management system. However, most of the current health care systems are still facing major obstacles and are lacking in some of these areas. This is where decentralized, secure, and scalable databases, most notably blockchains, play critical roles in addressing these requirements without compromising security, thereby attracting considerable interest within the health care community. A blockchain can be maintained and widely distributed using a large network of nodes, mostly computers, each of which stores a full replica of the data. A blockchain protocol is a set of predefined rules or procedures that govern how the nodes interact with the network, view, verify, and add data to the ledger. OBJECTIVE: In this article, we aim to explore blockchain technology, its framework, current applications, and integration with other innovations, as well as opportunities in diverse areas of health care and clinical research, in addition to clarifying its future impact on the health care ecosystem. We also elucidate 2 case studies to instantiate the potential role of blockchains in health care. METHODS: To identify related existing work, terms based on Medical Subject Headings were used. We included studies focusing mainly on health care and clinical research and developed a functional framework for implementation and testing with data. The literature sources for this systematic review were PubMed, Medline, and the Cochrane library, in addition to a preliminary search of IEEE Xplore. RESULTS: The included studies demonstrated multiple framework designs and various implementations in health care including chronic disease diagnosis, management, monitoring, and evaluation. We found that blockchains exhibit many promising applications in clinical trial management such as smart-contract application, participant-controlled data access, trustless protocols, and data validity. Electronic health records (EHRs), patient-centered interoperability, remote patient monitoring, and clinical trial data management were found to be major areas for blockchain usage, which can become a key catalyst for health care innovations. CONCLUSIONS: The potential benefits of blockchains are limitless; however, concrete data on long-term clinical outcomes based on blockchains powered and supplemented by AI and IoT are yet to be obtained. Nonetheless, implementing blockchains as a novel way to integrate EHRs nationwide and manage common clinical problems in an algorithmic fashion has the potential for improving patient outcomes, health care experiences, as well as the overall health and well-being of individuals.

Microsurgical and histological identification and definition of an interdural incision zone in the dorsolateral cavernous sinus.

OBJECTIVES: The anatomy of the cavernous sinus is described controversially in a number of publications. In the present cadaveric study, the architecture of the dorsolateral wall of the cavernous sinus is studied microsurgically and histologically. MATERIALS AND METHODS: Twenty cadaveric skulls have been dissected through a classical surgical frontotemporal approach. The temporal skull base was flattened and anatomical landmarks like the meningo-orbital band, superior orbital fissure, foramina rotundum, ovale, and spinosum were identified. Lateral of the trigeminal foramina, the dura was cut and the periosteal dural layer was separated from the meningeal layer, identifying an interdural zone. The length and the extent of this zone were evaluated. The dural architecture of the interdural incision zone was examined histologically. RESULTS: In all specimens, two dural layers lateral of the trigeminal foramina could be separated. The identified interdural incision zone extended in a length of 3.8-6.4 cm in the antero-posterior direction. The zone could be followed medially to the superior orbital fissure for 5.3 mm and lateral of the foramen spinosum for 6.4 mm. The separation of the dural layers allowed the approach to the superior border of the cavernous sinus through this interdural incision zone. The histological analysis of the interdural incision zone showed clearly the existence of two dural layers. CONCLUSIONS: The architecture of the temporal-fossa-dura allows the microsurgical separation of two meningeal dural layers through a length of 5-6 cm next to the trigeminal foramina. Opening this interdural incision zone allowed exploring the superior border of the cavernous sinus.

Associations of collagen type I α2 polymorphisms with the presence of intracranial aneurysms in patients from Germany.

OBJECTIVE: Subarachnoid hemorrhage from ruptured intracranial aneurysms is associated with a severe prognosis. Preventive treatment of unruptured intracranial aneurysms is possible and recommended. However, the identification of risk patients by genetic analyses is not possible because of lack of candidate genes. Collagen type I α2 (COL1A2) has been associated with the presence of aneurysms in patients from Japan, China, and Korea. In this study, we investigate whether COL1A2 is a possible aneurysm candidate gene in the German population. METHODS: Patients admitted with intracranial aneurysms to our department and collaborating departments were enrolled. Three single-nucleotide polymorphisms (SNPs) of the COL1A2 gene, namely rs42524 in exon 28, rs1800238 in exon 32, and rs2621215 in intron 46 were investigated using restriction enzymes and sequencing. HapMap data were used for comparison of allelic frequencies with the normal population by χ2 test to identify significant associations between genotypes and the presence of aneurysms. RESULTS: Two hundred sixty-nine patients were enrolled into the study. There was a significant correlation with the presence of aneurysms for the GC allele of the SNP rs42524 in exon 28 (P = .02). The other polymorphisms did not show significant correlations. CONCLUSIONS: The COL1A2 gene is associated with intracranial aneurysms in a subset of the German population. However, it is not responsible for the majority of aneurysms, and further candidate genes need to be identified to develop sensitive genetic screening for patients at risk.

Impact of pre-hospital antithrombotic medication on the outcome of chronic and acute subdural hematoma.

INTRODUCTION: Antithrombotic medication has proven efficacy in the treatment and prevention of cardiovascular and cerebrovascular diseases. A major disadvantage is the increased incidence of cerebral hemorrhages such as subdural hematomas (SDH). The impact of antithrombotic therapy on the outcome of subdural hematoma is not well characterized to date. MATERIALS AND METHODS: We retrospectively analyzed patients with subdural hematomas admitted to our hospital between 2005 and 2009. Antithrombotic medication, as well as other risk factors (age, sex, and preexisting diseases) were statistically analyzed in 476 consecutive patients for an independent association with inferior outcome, such as recurrent hematoma or in-hospital death. The patients had been evaluated and treated according to clinical standards for the management of severe head injury and were divided into groups with chronic SDH (cSDH) and acute SDH (aSDH), respectively. RESULTS: Of 312 patients with aSDH, 71 (22.8%) patients had at least one recurrence and 41 (13.1%) patients died in hospital. In the aSDH group, both the recurrence and the mortality were associated with anticoagulant therapy and with platelet aggregation inhibition. In the group of 163 patients with cSDH, 40 (24.5%) patients had a recurrence and 13 (7.9%) patients died within 9 weeks. Neither the application of platelet aggregation inhibitors nor the anticoagulant therapy were associated with recurrence or in-hospital mortality in this group. CONCLUSION: Our results clearly indicate that prehospital antithrombotic therapy was independently associated with inferior outcome of patients with aSDH, while no association for patients with cSDH was observed.

Acetylsalicylic acid inhibits α,ß-meATP-induced facilitation of neck muscle nociception in mice--implications for acute treatment of tension-type headache.

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. This animal experimental model is suggested to be appropriate for investigating pathophysiological mechanisms in tension-type headache. It was hypothesized that d-lysine acetylsalicylic acid (ASA, aspirin®) reverses this α,ß-meATP effect. Facilitation of neck muscle nociceptive processing was induced via bilateral infusion of α,ß-meATP into semispinal neck muscles (100 nM, 20 µl each) in 42 anesthetized mice. Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation. The hypothesis was addressed by subsequent (15, 30, 60 mg/kg) and preceding (60 mg/kg) intraperitoneal ASA injection. Saline served as control to ASA solution. Subsequent ASA dose-dependently reversed α,ß-meATP-induced reflex facilitation and was the most prominent with 60 mg/kg. Preceding 60 mg/kg ASA prevented reflex facilitation. Cyclooxygenases are involved in nociceptive transmission. Former experiments showed that unspecific inhibition of cyclooxygenases does not alter the α,ß-meATP effect. This suggests a specific mode of action of ASA. The concept is accepted that neck muscle nociception is involved in the pathophysiology of tension-type headache. Thus, objective proof of ASA effects in this experimental model may emphasize its major role in pharmacological treatment of tension-type headache attacks.

Inhibition of nNOS prevents and inhibition of iNOS reverses α,ß-meATP-induced facilitation of neck muscle nociception in mice.

Infusion of α,ß-methylene ATP (α,ß-meATP) into murine neck muscle facilitates brainstem nociception. Unspecific nitric oxide synthase (NOS) inhibition prevents and reverses this sensitization. It is unclear whether neuronal (nNOS), inducible (iNOS) or endothelial NOS isoenzymes are involved in this α,ß-meATP effect. Hypothesized involvement of nNOS isoenzyme was addressed by preceding (0.5, 1, and 2 mg/kg) and subsequent (2 mg/kg) intraperitoneal injection of the nNOS-inhibitor NPLA. iNOS involvement was addressed by subsequent, intraperitoneal administration of the iNOS-inhibitor 1400 W (2 mg/kg). Brainstem nociception was monitored by the jaw-opening reflex elicited via electrical tongue stimulation in 45 anesthetized mice. Preceding NPLA dose-dependently prevented α,ß-meATP-induced reflex facilitation. Whereas subsequent inhibition of nNOS showed no effect, iNOS inhibition by 1400 W significantly reversed reflex facilitation. Data provide evidence that nNOS plays a major role in induction and iNOS in maintenance of facilitation in neck muscle nociception. Divergent roles of NOS isoenzymes may promote research on target specific treatment for headache and neck muscle pain.

Inhibition of nitric oxide synthases prevents and reverses alpha,beta-meATP-induced neck muscle nociception in mice.

INTRODUCTION: Tension-type headache (TTH) is associated with noxious input from neck muscles. Intravenous administration of the unspecific nitric oxide synthase inhibitor L-NMMA in chronic TTH patients caused analgesia and reduction of neck muscle tenderness. METHODS: The unspecific nitric oxide synthase inhibitor L-NMMA was applied in an experimental model for neck muscle nociception in anesthetized mice (N = 25). RESULTS: Local injection of α,ß-meATP into semispinal neck muscles induced sustained facilitation of brainstem nociception as monitored by the jaw-opening reflex. Preceding intraperitoneal administration of L-NMMA (0.05, 0.1, 1 mg/kg) prevented reflex facilitation evoked by α,ß-meATP in a dose-dependent manner. Intraperitoneal injection of L-NMMA subsequent to intramuscular α,ß-meATP application reversed established brainstem reflex facilitation back to baseline values. DISCUSSION: Both experiments with preceding and subsequent L-NMMA indicate the involvement of nitric oxide synthases in the induction and maintenance of facilitation. However, future experiments will have to address the involvement of various isoenzymes in order to provide for new therapeutic concepts in TTH.

Analgesic and antinociceptive effects of peripheral nerve neurostimulation in an advanced human experimental model.

Electrical peripheral nerve neurostimulation (PNS) is reported to be an effective pain treatment. An objective proof of antinociceptive effect is lacking. The human experimental study addressed PNS effects on nociception and pain by electrophysiology and psychophysics. In 23 healthy volunteers, 39 sessions were conducted. Three experiments (PNS ipsilateral, PNS contralateral, Control) consisted of 13 sessions each. Conditioning PNS (100 Hz) of left (PNS ipsilateral) or right (PNS contralateral) superficial radial nerve trunk evoked non-painful, tingling sensations on the hand dorsum. Local cutaneous anesthesia at PNS site provided for preferential nerve trunk stimulation. Cortical laser-evoked potentials (LEP) after painful stimulation at left hand dorsum were recorded together with mechanical and thermal perception thresholds at the same site before (T1), during (T2), and after (T3) PNS or a no stimulation period (Control). Mechanical and thermal perception decreased in the anesthetized area. Late LEP amplitude decreased independently of PNS site. Exclusively under ipsilateral PNS, N2 latency increased and laser ratings decreased. Mechanical detection threshold transiently increased during ipsilateral PNS at hand dorsum. PNS induced strong reduction of mechanical perception due to peripheral collision of orthodromic (test stimulus) and antidromic (PNS) selective Abeta fiber excitation. Delay of N2 component and reduction of laser pain were specific to ipsilateral PNS. Divergent and common effects of ipsilateral and contralateral PNS suggest a combination of peripheral and central antinociceptive mechanisms. The study in man documents inhibition of nociception and pain by PNS and provides with an experimental model for future objectives in neuromodulation.

Molecular MRI of cerebral venous sinus thrombosis using a new fibrin-specific MR contrast agent.

BACKGROUND AND PURPOSE: Imaging of cerebral vein thrombosis is still challenging. Currently, diagnosis is based on CT venography and MRI including MRA and conventional digital subtraction angiography. However, especially in chronic cases, each method has shown its limitations. Newer strategies for MRI are found on molecular imaging using targeted contrast agents. The aim of this study was to prove the feasibility of a novel fibrin-targeted MR contrast agent (EP-2104R; EPIX Pharmaceuticals) for selective imaging of sinus venous thrombosis in an animal model. METHODS: Thrombosis of the superior sagittal sinus with human blood was induced in 6 pigs using a combined microsurgical and interventional approach. MRI was then performed before and up to 120 minutes after injection of 4 micromol/kg body weight EP-2104R. Molecular imaging was performed with a 3-dimensional high-resolution T1-weighted gradient echo sequence. Time courses of signal-to-noise ratio and contrast-to-noise ratio were analyzed. Thrombi were then surgically removed and the Gadolinium concentration was assessed. RESULTS: In all cases the thrombosis could be successfully induced; the complete MR protocol could be performed in 5 animals. In these cases the thrombi showed selective enhancement after injection of the molecular contrast agent. However, a continuous contrast-to-noise ratio increase was seen up to 120 minutes after contrast administration, achieving a contrast-to-noise ratio of 14.2+/-0.7 between clot and the blood pool. CONCLUSIONS: The novel fibrin-targeted molecular MR contrast EP-2104R allows selective and high-contrast imaging of cerebral sinus vein thrombosis in an animal model.

Inhibition of platelet aggregation by grafting RGD and KGD sequences on the structural scaffold of small disulfide-rich proteins.

Disintegrins represent a group of disulfide-rich peptides ranging in size from 41 to over 80 residues and are antagonists of several integrin receptors. Disintegrins containing an RGD or KGD sequence are potent inhibitors of platelet aggregation as they block the binding of fibrinogen to alpha(IIb)beta(3) integrin. The high affinity binding to alpha(IIb)beta(3) in comparison to short linear peptides has been attributed to the localisation of the RGD or KGD sequence within a defined three-dimensional structure. Cystine knot microproteins are members of another family of small disulfide-rich peptides that consist of only 28-40 amino acid residues. They display numerous biological activities depending on the peptide sequence of loop regions that are fixed on a structural scaffold that is stabilised by three knot-forming disulfide bonds. In the present study we grafted RGD and KGD containing peptide sequences with seven and 11 amino acids, respectively, into two cystine knot microproteins, the trypsin inhibitor EETI-II and the melanocortin receptor binding domain of the human agouti-related protein AGRP, as well as into the small disintegrin obtustatin. The engineered proteins were much more potent to inhibit the fibrinogen binding, alpha(IIb)beta(3) activation and platelet aggregation when compared to the grafted peptides. Differences that were observed between the engineered proteins indicate the importance of the structural scaffold and the amino acids neighbouring the grafted peptide sequences.

Virtual placement of posterior C1-C2 transarticular screw fixation.

We wanted to evaluate how often safe and effective posterior C1-C2 transarticular screw placement is realizable when it is performed according to guidelines given in the literature. In 50 adult patients, computerized tomography scan data from C0 to C3 were transformed into a 3D spine model. Virtually, bilateral screws were placed from the medial third of the C2-C3 facet joint towards the rim of the C1 anterior arc parallel to midline. Three categories of virtual screw position were rated: optimal (virtual screw inside the C2 pars interarticularis, transversing the middle third of the atlantoaxial joint, and sparing the vertebral artery canal), suboptimal (virtual screw violating the C2 pars interarticularis, and/or transversing the lower or upper third of the C1-C2 joint, and sparing vertebral artery canal), and unacceptable (virtual screw breaching the vertebral artery canal). Optimal placement was seen in 74, suboptimal placement in 11, and unacceptable locations in 15 sites. We conclude that due to the variability of the anatomy of the upper cervical spine, optimal transarticular C1-C2 screw placement is not possible in up to 26%, and even hazardous in up to 15%.

Platelet and leukocyte activation correlate with the severity of septic organ dysfunction.

This study was conducted to investigate the extent of platelet-leukocyte adhesion and platelet, monocyte, and neutrophil activation in septic patients and to analyze whether these variables correlate with the severity of sepsis. Forty-seven patients consecutively admitted to the operative ICU of a University Medical Centre and 12 control patients prior to elective surgery were included in this prospective cohort study. Patients were evaluated daily for sepsis criteria and sepsis-associated organ failure assessment (SOFA) score was used to describe the extent of sepsis-associated organ failure. Indicators for cell activation (CD62P on platelets and CD11b on neutrophils and monocytes) and binding of platelets to neutrophils and monocytes were analyzed by flow cytometry. CD62P was increased on platelets from patients with sepsis compared with patients who did not have sepsis. Patients with sepsis also had higher CD11b expression on neutrophils and monocytes. Statistical analyses revealed a positive correlation between platelet CD62P expression and severity of sepsis, as well as a positive correlation between the SOFA score and CD11b on monocytes. No correlation was found between the SOFA score and CD11b on neutrophils. Higher values for platelet-neutrophil adhesion were observed in patients with uncomplicated sepsis compared either with controls or to patients with septic shock. An inverse relation between severity of sepsis and extent of platelet-neutrophil adhesion was also obvious from correlation analysis. The results indicate that flow cytometry can be used to measure these parameters of cell activation in sepsis and that activation of platelets and monocytes as well as adhesion of platelets to neutrophils does play a role in the development of organ dysfunction.