An in vitro experimental investigation of oscillatory flow in the cerebral aqueduct.

This in vitro study aims at clarifying the relation between the oscillatory flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a narrow conduit connecting the third and fourth ventricles, and the corresponding interventricular pressure difference. Dimensional analysis is used in designing an anatomically correct scaled model of the aqueduct flow, with physical similarity maintained by adjusting the flow frequency and the properties of the working fluid. The time-varying pressure difference across the aqueduct corresponding to a given oscillatory flow rate is measured in parametric ranges covering the range of flow conditions commonly encountered in healthy subjects. Parametric dependences are delineated for the time-averaged pressure fluctuations and for the phase lag between the transaqueductal pressure difference and the flow rate, both having clinical relevance. The results are validated through comparisons with predictions obtained with a previously derived computational model. The parametric quantification in this study enables the derivation of a simple formula for the relation between the transaqueductal pressure and the stroke volume. This relationship can be useful in the quantification of transmantle pressure differences based on non-invasive magnetic-resonance-velocimetry measurements of aqueduct flow for investigation of CSF-related disorders.

Diffusion-weighted imaging of the orbit.

Orbital lesions compose a heterogeneous group of pathologies that often present with non-specific imaging findings on conventional magnetic resonance imaging (MRI) sequences (T1-and T2-weighted). Accordingly, the application of diffusion MRI offers an opportunity to further distinguish between lesions along this spectrum. Diffusion-weighted imaging (DWI) represents the simplest and most frequent clinically utilised diffusion imaging technique. Recent advances in DWI techniques have extended its application to the evaluation of a wider spectrum of neurological pathology, including orbital lesions. This review details the manifestations of select orbital pathology on DWI and underscores specific situations where diffusion imaging allows for increased diagnostic sensitivity compared to more conventional MRI techniques. These examples also describe preferred management for orbital lesions identified by DWI.

A one-dimensional model for the pulsating flow of cerebrospinal fluid in the spinal canal.

The monitoring of intracranial pressure (ICP) fluctuations, which is needed in the context of a number of neurological diseases, requires the insertion of pressure sensors, an invasive procedure with considerable risk factors. Intracranial pressure fluctuations drive the wave-like pulsatile motion of cerebrospinal fluid (CSF) along the compliant spinal canal. Systematically derived simplified models relating the ICP fluctuations with the resulting CSF flow rate can be useful in enabling indirect evaluations of the former from non-invasive magnetic resonance imaging (MRI) measurements of the latter. As a preliminary step in enabling these predictive efforts, a model is developed here for the pulsating viscous motion of CSF in the spinal canal, assumed to be a linearly elastic compliant tube of slowly varying section, with a Darcy pressure-loss term included to model the fluid resistance introduced by the trabeculae, which are thin collagen-reinforced columns that form a web-like structure stretching across the spinal canal. Use of Fourier-series expansions enables predictions of CSF flow rate for realistic anharmonic ICP fluctuations. The flow rate predicted using a representative ICP waveform together with a realistic canal anatomy is seen to compare favourably with in vivo phase-contrast MRI measurements at multiple sections along the spinal canal. The results indicate that the proposed model, involving a limited number of parameters, can serve as a basis for future quantitative analyses targeting predictions of ICP temporal fluctuations based on MRI measurements of spinal-canal anatomy and CSF flow rate.

Effect of Normal Breathing on the Movement of CSF in the Spinal Subarachnoid Space.

BACKGROUND AND PURPOSE: Forced respirations reportedly have an effect on CSF movement in the spinal canal. We studied respiratory-related CSF motion during normal respiration. MATERIALS AND METHODS: Six healthy subjects breathed at their normal rate with a visual guide to ensure an unchanging rhythm. Respiratory-gated phase-contrast MR flow images were acquired at 5 selected axial planes along the spine. At each spinal level, we computed the flow rate voxelwise in the spinal canal, together with the associated stroke volume. From these data, we computed the periodic volume changes of spinal segments. A phantom was used to quantify the effect of respiration-related magnetic susceptibility changes on the velocity data measured. RESULTS: At each level, CSF moved cephalad during inhalation and caudad during expiration. While the general pattern of fluid movement was the same in the 6 subjects, the flow rates, stroke volumes, and spine segment volume changes varied among subjects. Peak flow rates ranged from 0.60 to 1.59 mL/s in the cervical region, 0.46 to 3.17 mL/s in the thoracic region, and 0.75 to 3.64 mL/s in the lumbar region. The differences in flow rates along the canal yielded cyclic volume variations of spine segments that were largest in the lumbar spine, ranging from 0.76 to 3.07 mL among subjects. In the phantom study, flow velocities oscillated periodically during the respiratory cycle by up to 0.02 cm/s or 0.5%. CONCLUSIONS: Respiratory-gated measurements of the CSF motion in the spinal canal showed cyclic oscillatory movements of spinal fluid correlated to the breathing pattern.

Drag reduction of three-dimensional bodies by base blowing with various gas densities.

This study reveals that injecting a light fluid of density ρ_{b} in the recirculating bubble of a bluff body at Re≈6.4×10^{4} has a greater drag reduction potential than blowing fluid of a density greater than or equal to that of the free stream ρ. It is found that the maximum drag reduction scales as (ρ_{b}/ρ)^{-1/6}. This power law combines the ability of the recirculating bubble to diffuse the injected momentum and the effectiveness of the injection to increase the recirculating bubble length.

DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.

Recent genome-wide association studies of Huntington's disease (HD) primarily highlighted genes involved in DNA damage repair mechanisms as modifiers of age at onset and disease severity, consistent with evidence that more DNA repair genes are being implicated in late age-onset neurodegenerative diseases. This provides an exciting opportunity to advance therapeutic development in HD, as these pathways have already been under intense investigation in cancer research. Also emerging are the roles of other polyglutamine disease proteins in DNA damage repair mechanisms. A potential universal trigger of oxidative DNA damage shared in these late age-onset diseases is the increase of reactive oxygen species (ROS) in human aging, defining an age-related mechanism that has defied other hypotheses of neurodegeneration. We discuss the potential commonality of DNA damage repair pathways in HD and other neurodegenerative diseases. Potential targets for therapy that may prove beneficial across many of these diseases are also identified, defining nodes in the ataxia telangiectasia-mutated (ATM) complex, mismatch repair, and poly ADP-ribose polymerases (PARPs).

Subject-Specific Studies of CSF Bulk Flow Patterns in the Spinal Canal: Implications for the Dispersion of Solute Particles in Intrathecal Drug Delivery.

BACKGROUND AND PURPOSE: Recent flow dynamics studies have shown that the eccentricity of the spinal cord affects the magnitude and characteristics of the slow bulk motion of CSF in the spinal subarachnoid space, which is an important variable in solute transport along the spinal canal. The goal of this study was to investigate how anatomic differences among subjects affect this bulk flow. MATERIALS AND METHODS: T2-weighted spinal images were obtained in 4 subjects and repeated in 1 subject after repositioning. CSF velocity was calculated from phase-contrast MR images for 7 equally spaced levels along the length of the spine. This information was input into a 2-time-scale asymptotic analysis of the Navier-Stokes and concentration equations to calculate the short- and long-term CSF flow in the spinal subarachnoid space. Bulk flow streamlines were shown for each subject and position and inspected for differences in patterns. RESULTS: The 4 subjects had variable degrees of lordosis and kyphosis. Repositioning in 1 subject changed the degree of cervical lordosis and thoracic kyphosis. The streamlines of bulk flow show the existence of distinct regions where the fluid particles flow in circular patterns. The location and interconnectivity of these recirculating regions varied among individuals and different positions. CONCLUSIONS: Lordosis, kyphosis, and spinal cord eccentricity in the healthy human spine result in subject-specific patterns of bulk flow recirculating regions. The extent of the interconnectivity of the streamlines among these recirculating regions is fundamental in determining the long-term transport of solute particles along the spinal canal.

CT and MRI features in Bipolaris fungal sinusitis.

Bipolaris is an increasingly recognized cause of fungal sinusitis. Reports of imaging features are sparse. Our purpose was to review the imaging features in patients with Bipolaris fungal sinusitis. A review of our data showed seven patients with culture-proven Bipolaris fungal sinusitis. Computed tomography of the paranasal sinuses in all the patients and MRI in five patients were analysed for the location, nature, extent of the disease and density/signal characteristics on CT/MRI. The sphenoid and posterior ethmoid sinuses were most often involved (six of seven), followed by the anterior ethmoid sinus (five of seven), frontal sinus (four of seven) and maxillary sinus (three of seven) involvement. Five of seven cases had bilateral disease. Secretions were seen to fill the sinus and were expansile in nature in six of seven cases. Bony erosion was noted in all the patients. Air-fluid levels and bony sclerosis were rarely seen. Computed tomography showed central hyperdensity in all the cases. In the corresponding MR images (n = 5), the sinus contents appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Extension into the nasal cavity was found in six of seven cases. Five of seven cases had intracranial (extradural) spread. Intraorbital extension was seen in three of seven cases, with associated optic nerve compression in two. All the patients responded to surgical debridement, and systemic antifungal therapy was not required. Bipolaris fungal sinusitis typically presents with an allergic fungal sinusitis picture with expansile sinus opacification and bony erosions. There is central hyperdensity on CT scan, which appears hyperintense on T1-weighted and hypointense on T2-weighted MR images.

Axisymmetric bubble pinch-off at high Reynolds numbers.

Analytical considerations and potential-flow numerical simulations of the pinch-off of bubbles at high Reynolds numbers reveal that the bubble minimum radius, rn, decreases as tau proportional to r2n sqrt[1lnr2n], where tau is the time to break up, when the local shape of the bubble near the singularity is symmetric. However, if the gas convective terms in the momentum equation become of the order of those of the liquid, the bubble shape is no longer symmetric and the evolution of the neck changes to a rn proportional to tau1/3 power law. These findings are verified experimentally.

A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema.

BACKGROUND: Human corticotropin-releasing factor (hCRF) is an endogenous peptide responsible for the secretion and synthesis of corticosteroids. In animal models of peritumoral brain edema, hCRF has significant anti-edematous action. This effect, which appears to be independent of the release of adrenal steroids, appears mediated by a direct effect on endothelial cells. We conducted a feasibility and phase I study with hCRF given by continuous infusion to patients with brain metastasis. PATIENTS AND METHODS: Peritumoral brain edema documented by MRI and the use of either no steroids or stable steroid doses for more than a week were required. MRIs were repeated at completion of infusion and estimations by dual echo-image sequence (Proton density and T2-weighted images) of the amount of peritumoral edema were performed. The study was performed in two stages. In the feasibility part, patients were randomized to receive either 0.66 or 1 microgram/kg/h of hCRF or placebo over 24 hours. The second part was a dose finding study of hCRF over 72 hours at escalating doses. RESULTS: Seventeen patients were enrolled; only one was receiving steroids (stable doses) at study entrance; dose-limiting toxicity (hypotension) was observed at 4 micrograms/kg/h x 72 hours in two out of four patients, while zero of five patients treated at 2 micrograms/kg/h developed dose-limiting toxicities. Flushing and hot flashes were also observed. Improvement of neurological symptoms and/or exam were seen in 10 patients. Only small changes were detected by MRI. Improvement in symptoms did not correlate with changes in cortisol levels, and changes in cortisol levels were not correlated with changes in peritumoral edema. CONCLUSIONS: hCRF is well tolerated in doses up to 2 micrograms/kg/h by continuous infusion x 72 hours. Hypotension limits administration of higher doses. The observation of clinical benefit in the absence of corticosteroids suggests hCRF may be an alternative to steroids for the treatment of patients with peritumoral brain edema. Further exploration of this agent in efficacy studies is warranted.

MR of parenchymal spinal cord signal change as a sign of active advancement in clinically progressive posttraumatic syringomyelia.

Extensive MR signal change in the craniad spinal cord parenchyma was found to be an ancillary sign of disease advancement in three patients with clinically progressive posttraumatic syringomyelia. This craniad margin of parenchymal spinal cord T2 hyperintensity resolved after cystoperitoneal shunt placement. There was a concomittant reduction or disappearance of the cyst in each instance, a halt in the progression of neurologic deficit, and some reversal of signs and symptoms.

Evaluación clínica de niños diabéticos relacionada al estado de salud bucal / Clinical evaluation of diabetic children in relation to oral health status

La diabetes mellitus es una enfermedad crónica y sistémica que puede ocasionar complicaciones irreversibles. En este trabajo se presenta un análisis del estado clínico de niños diabéticos y su relación con los exámenes de laboratorio y de salud bucal que ellos presentaban en el momento del estudio. Se determinaron glucosa por el método enzimático específico, y hemoglobina glicosilada por el método cromatográfico, y los índices gingival y de placa bacteriana según Loe y Silness. Estos niños llevan un adecuado control metabólico por cuanto existe ausencia de lesiones microvasvulares. La diferencia entre edad ósea y edad cronológica se observa cuando la diabetes se asocia a tiroiditis. Además, estos niños prsentan elevado número de caries dental y alto riesgo de gingivitis, aspectos que estarían poco relacionados linealmente con la antiguedad de la enfermedad. El examen bioquímico de la saliva no reveló correlación estadística entre glucemia, hemoglobina glicolsilada y glucosa salival. Es fundamental insistir sobre medidas preventivas destinadas a mejorar el estado de salud bucal de los pacientes diabéticos

MRI of cervical facet dislocation.

The MRI examinations of eight patients with cervical vertebral dislocation demonstrated by conventional radiography were reviewed. All patients had axial and sagittal T1- and T2-weighted imaging on a 1.5-T Unit. This revealed unilateral partial facet dislocation (in two patients), bilateral partial facet dislocation (in two), unilateral complete dislocation (in two) and bilateral complete facet dislocation (in two). In six patients there was cord contusion, three had focal disc protrusions and four unilateral absence of normal flow void in one of the cervical vertebral arteries. In all cases, the dislocated facets were shown well on the far-lateral sagittal images.

Long-term response to crisnatol mesylate in patients with glioma.

A total of 26 patients (6 with anaplastic astrocytoma; 20 with glioblastoma) were treated with crisnatol mesylate. All patients had residual or progressive disease following surgery and standard radiotherapy; nine patients had prior chemotherapy. Crisnatol was administered as a 72-hour infusion every 21 days at a starting dose of 2250 mg/m2. Two patients who had not received prior chemotherapy achieved a complete response and remain in continuous complete remission over seven and six years, respectively, post-diagnosis. Two other patients remained stable on crisnatol for 10 months before disease progression. One patient with mixed oligodendroglioma/glioblastoma progressed after 12 months on crisnatol. He survives at 7 years post-diagnosis, with Karnofsky Performance Status of 60 following other therapies. One patient with anaplastic astrocytoma stopped treatment by request after 10 months and remains stable 64 months post diagnosis. Seventeen evaluable patients, including nine patients with prior chemotherapy, progressed after 2-9 courses of therapy. Median survival is 9.25 months, with a one year survival rate of 30% and 2 years survival rate of 17%. Neurotoxicity was acute and dose-limiting. Side effects were tolerable and limited to duration of infusion. Two complete, long-lasting responses to crisnatol mesylate in patients with progressive malignant glioma are encouraging results and warrant further investigation.

MR of disc protrusion engendered by infectious spondylitis.

PURPOSE: The purpose of this study was to determine if infection-related disc protrusion formed a component of the perispinous/epidural mass in patients with intervertebral disc infection. METHOD: A retrospective review was undertaken of 16 consecutive patients with intervertebral disc space infection who were referred for gadolinium-enhanced MRI. Possible correlation was sought between disc infection and the presence of associated posterior disc protrusion as determined by MRI. RESULTS: Of the 16 infected discs, 10 cases were in the lumbosacral spine, 3 in the thoracic spine, and 3 in the cervical spine. Four cases had isolated posteriorly directed disc protrusion, and 12 showed both posterior and anterior disc protrusions. The infection in patients with disc protrusion was related to Staphylococcus aureus in 14 patients, Salmonella enteritidis in 1, and Streptococcus pneumoniae in 1. CONCLUSION: This study showed that disc protrusion occurred in combination with disc space infections. Local factors such as the secretion by hyaluronidase from Staphylococcus aureus may play an important role in causing focal disc protrusion. The clinical importance of this finding is in the recognition that a significant part of the compromise of the spinal canal in cases of disc infection can be related to disc fragments engendered by the infectious process.

Lumbosacral spine: early and delayed MR imaging after administration of an expanded dose of gadopentetate dimeglumine in healthy, asymptomatic subjects.

PURPOSE: To determine normal magnetic resonance (MR) imaging enhancement characteristics of the lumbosacral spine after intravenous administration of an expanded dose of gadopentetate dimeglumine. MATERIALS AND METHODS: T1-weighted MR images of the lumbosacral spine were acquired before and after injection of 0.3 mmol/kg gadopentetate dimeglumine in 12 healthy subjects (eight men, four women; age range, 22-57 years). RESULTS: In 10 (91%) of the 11 subjects who completed the investigation, multifocal linear enhancement within the thecal sac that generally extended from the conus to the nerve-root sheaths was demonstrated. In all cases, enhancement was seen in the facet joints and the intervertebral disks parallel to the vertebral end-plates. CONCLUSION: After an expanded dose of intravenous gadopentetate dimeglumine, multiple intrathecal and extrathecal structures were enhanced. Recognition of normal enhancement patterns after an expanded gadopentetate dimeglumine dose is important because such enhancement after routine injection of 0.1 mmol/kg gadopentetate dimeglumine is often thought to indicate disease.