Characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging.

Recent advancements have been made toward understanding the diagnostic and therapeutic potential of cerebrospinal fluid (CSF) and related hydrodynamics. Increased understanding of CSF dynamics may lead to improved detection of central nervous system (CNS) diseases and optimized delivery of CSF based CNS therapeutics, with many proposed therapeutics hoping to successfully treat or cure debilitating neurological conditions. Before significant strides can be made toward the research and development of interventions designed for human use, additional research must be carried out with representative subjects such as non-human primates (NHP). This study presents a geometric and hydrodynamic characterization of CSF in eight cynomolgus monkeys (Macaca fascicularis) at baseline and two-week follow-up. Results showed that CSF flow along the entire spine was laminar with a Reynolds number ranging up to 80 and average Womersley number ranging from 4.1-7.7. Maximum CSF flow rate occurred ~25 mm caudal to the foramen magnum. Peak CSF flow rate ranged from 0.3-0.6 ml/s at the C3-C4 level. Geometric analysis indicated that average intrathecal CSF volume below the foramen magnum was 7.4 ml. The average surface area of the spinal cord and dura was 44.7 and 66.7 cm2 respectively. Subarachnoid space cross-sectional area and hydraulic diameter ranged from 7-75 mm2 and 2-3.7 mm, respectively. Stroke volume had the greatest value of 0.14 ml at an axial location corresponding to C3-C4.

Cerebellar tonsil ectopia measurement in type I Chiari malformation patients show poor inter-operator reliability.

BACKGROUND: Type 1 Chiari malformation (CM-I) has been historically defined by cerebellar tonsillar position (TP) greater than 3-5 mm below the foramen magnum (FM). Often, the radiographic findings are highly variable, which may influence the clinical course and patient outcome. In this study, we evaluate the inter-operator reliability (reproducibility) of MRI-based measurement of TP in CM-I patients and healthy controls. METHODS: Thirty-three T2-weighted MRI sets were obtained for 23 CM-I patients (11 symptomatic and 12 asymptomatic) and 10 healthy controls. TP inferior to the FM was measured in the mid-sagittal plane by seven expert operators with reference to McRae's line. Overall agreement between the operators was quantified by intraclass correlation coefficient (ICC). RESULTS: The mean and standard deviation of cerebellar TP measurements for asymptomatic (CM-Ia) and symptomatic (CM-Is) patients in mid-sagittal plane was 6.38 ± 2.19 and 9.57 ± 2.63 mm, respectively. TP measurements for healthy controls was 0.48 ± 2.88 mm. The average range of TP measurements for all data sets analyzed was 7.7 mm. Overall operator agreement for TP measurements was relatively high with an ICC of 0.83. CONCLUSION: The results demonstrated a large average range (7.7 mm) of measurements among the seven expert operators and support that, if economically feasible, two radiologists should make independent measurements before radiologic diagnosis of CM-I and surgery is contemplated. In the future, an objective diagnostic parameter for CM-I that utilizes automated algorithms and results in smaller inter-operator variation may improve patient selection.

Clinical Course of a Patient With Kidney Failure Due to Isolated Bilateral Renal Extramedullary Plasmacytomas.

Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012. Precipitous kidney failure, anorexia, fatigue, and flank pain necessitated clinical follow-up that ultimately led to thorough imaging and bilateral kidney biopsy. Protein electrophoresis, immunohistochemistry, and immunofluorescence were all consistent with bilateral renal extramedullary plasmacytomas. Treatment recommendations are often limited to prior case successes; however, chemotherapy, radiation, and surgery are the mainstay of treatment. Although surgery or combined therapy provides the best results for patients, such options are unfeasible with bilateral kidney involvement. Therefore, a chemotherapy regimen, similar to that for multiple myeloma, was determined to be most reasonable. Treatment consisted of 4 cycles of a bortezomib, cyclophosphamide, and dexamethasone regimen. Three months following chemotherapy, kidney function returned to baseline levels.

Cardiac-Related Spinal Cord Tissue Motion at the Foramen Magnum is Increased in Patients with Type I Chiari Malformation and Decreases Postdecompression Surgery.

OBJECTIVE: Type 1 Chiari malformation (CM-I) is a craniospinal disorder historically defined by cerebellar tonsillar position greater than 3-5 mm below the foramen magnum (FM). This definition has come under question because quantitative measurements of cerebellar herniation do not always correspond with symptom severity. Researchers have proposed several additional radiographic diagnostic criteria based on dynamic motion of fluids and/or tissues. The present study objective was to determine if cardiac-related craniocaudal spinal cord tissue displacement is an accurate indicator of the presence of CM-I and if tissue displacement is altered with decompression. METHODS: A cohort of 20 symptomatic patients underwent decompression surgery. Fifteen healthy volunteers were recruited for comparison with the CM-I group. Axial phase-contrast magnetic resonance imaging (PC-MRI) measurements were collected before and after surgery at the FM with cranial-caudal velocity encoding and 20 frames per cardiac cycle with retrospective reconstruction. Spinal cord motion (SCM) at the FM was quantified based on the peak-to-peak integral of average spinal cord velocity. RESULTS: Tissue motion for the presurgical group was significantly greater than controls (P = 0.0009). Motion decreased after surgery (P = 0.058) with an effect size of -0.151 mm and a standard error of 0.066 mm. Postoperatively, no statistical difference from controls in bulk displacement at the FM was found (P = 0.200) after post hoc testing using the Tukey adjustment for multiple comparisons. CONCLUSIONS: These results support SCM measurement by PC-MRI as a possible noninvasive radiographic diagnostic for CM-I. Dynamic measurement of SCM provides unique diagnostic information about CM-I alongside static quantification of tonsillar position and other intracranial morphometrics.