Potentially reversible acute cerebellar toxicity associated with Minnelide

Minnelide is an experimental antineoplastic agent that is currently the subject of a phase 1 clinical trial for the treatment of pancreatic and gastrointestinal malignancies. In this study, we documented two cases of reversible acute cerebellar toxicity (REACT) associated with Minnelide and compared its radiological manifestations with other cerebellotoxic agents. Both patients had histories of progressive metastatic cancer and participated in a phase 1 clinical trial with Minnelide. They had an MRI examination including T2WI, FLAIR and SWI, axial and coronal DWI, and ADC map on admission and follow up. In each patient, the initial MRI demonstrated increased signal on FLAIR and restricted diffusion in the cerebellar cortex without involvement of deep cerebellar nuclei or supratentorial areas. The presenting symptoms and the majority of imaging findings resolved on follow up MRI. To our knowledge, Minnelide has shown an uncommon radiologic pattern of isolated cerebellar cortical involvement compared to other causes of cerebellar toxicity. Since this is a new medication, physicians' familiarity with the presenting symptoms and its temporal association with the imaging findings is important

Pseudo-Leptomeningeal Contrast Enhancement at 3T in Pediatric Patients Sedated by Propofol

Propofol is a cerebral vasoconstrictor that modulates cerebral perfusion by decreasing the metabolic rate of oxygen. Because younger children often undergo intravenous sedation for MR imaging, this study set out to evaluate the degree of leptomeningeal contrast enhancement on 3T postcontrast brain MR imaging and to determine whether this phenomenon relates to sequence, sedation dosage, or patient age or weight. During a 2-year period, of 152 children 1-5 years of age who underwent MR imaging, 43 were included for MRI review. Of these, 37 underwent postcontrast imaging with either solely gradient-echo T1WI ( = 20) or spin-echo T1WI ( = 17); notably, 6 patients underwent both sequences. Three neuroradiologists separately graded the degree of leptomeningeal contrast enhancement (grades 0-3) that was correlated with various factors and calculated the interobserver reliability. For the 43 patients, the mean patient age was 3.1 ± 1.4 years. The leptomeningeal contrast-enhancement grade was significantly greater ( < .0001) on spin-echo T1WI (1.9-2.1) versus gradient-echo TIWI (1.2-1.4). Patient weight ( = -0.366 to -.418, = .003-.01) and age ( = -0.315 to -0.418, = .004-.032) moderately and inversely correlated with the leptomeningeal contrast-enhancement grade, while the propofol dosage, sedation duration, and time to T1WI post-contrast administration did not (each, > .05). The interobserver κ was strong regarding the leptomeningeal contrast-enhancement grade on both spin-echo T1WI (κ = 0.609-0.693, < .0001) and gradient-echo TIWI (κ = 0.567-0.698, < .0001). Leptomeningeal contrast enhancement (or "pseudo"-leptomeningeal contrast enhancement) occurs with a greater frequency and degree on 3T postcontrast spin-echo T1WI relative to gradient-echo TIWI in younger children sedated with propofol and should not be mistaken for disease. This phenomenon may be more prominent with lower age or size and may arise from propofol-induced vascular smooth-muscle dilation

Transforaminal Lumbar Puncture: An Alternative Technique in Patients with Challenging Access

Interlaminar lumbar puncture and cervical puncture may not be ideal in all circumstances. Recently, we have used a transforaminal approach in selected situations. Between May 2016 and December 2017, twenty-six transforaminal lumbar punctures were performed in 9 patients (25 CT-guided, 1 fluoroscopy-guided). Seven had spinal muscular atrophy and were referred for intrathecal nusinersen administration. In 2, CT myelography was performed via transforaminal lumbar puncture. The lumbar posterior elements were completely fused in 8, and there was an overlying abscess in 1. The L1-2 level was used in 2; the L2-3 level, in 10; the L3-4 level, in 12; and the L4-5 level, in 2 procedures. Post-lumbar puncture headache was observed on 4 occasions, which resolved without blood patching. One patient felt heat and pain at the injection site that resolved spontaneously within hours. One patient had radicular pain that resolved with conservative treatment. Transforaminal lumbar puncture may become an effective alternative to classic interlaminar lumbar puncture or cervical puncture

Childhood Cerebral X-Linked Adrenoleukodystrophy: Diffusion Tensor Imaging Measurements for Prediction of Clinical Outcome after Hematopoietic Stem Cell Transplantation

BACKGROUND AND PURPOSE: DTI in cerebral X-linked adrenoleukodystrophy may demonstrate abnormalities in both affected and nonaffected WM; these values have not been studied serially after hematopoietic stem cell transplantation. The purpose of this study was to study pretransplant and posttransplant DTI parameters serially and ultimately to determine the ability of pretransplant DTI parameters to predict clinical outcome after HSCT in children with ALD. MATERIALS AND METHODS: Eight patients with posterior-pattern cerebral ALD underwent DTI at 3T before HSCT (T0), at 30-60 days (T1), 90-120 days (T2), 180 days (T3), and 1 year (T4) after HSCT. FA and MD were serially measured in 19 regions, and these measurements were compared with those in control patients. MR imaging severity (Loes) scores were recorded. Correlations were performed between DTI parameters and Loes scores, neurologic function scores, and several neuropsychologic scores. RESULTS: Both FA and MD in subjects differed significantly from that in controls at nearly every time point within cerebellar WM, callosal splenium, and parieto-occipital WM; FA alone was significantly different at each time point within the optic radiations, lateral geniculate, and the Meyer loop (P < .05). Loes scores at T0 correlated strongly with each clinical score at T4 (r = 0.771-0.986, P < .05). The only significant DTI correlation at T0 with a clinical score at T4 was callosal body FA with adaptive function (r = 0.976, P < .001). Correlating the change in DTI values with change in NFS (change between T0 and T4) showed that only MD within the optic radiations correlated strongly with NFS (r = 0.903, P < .05). CONCLUSIONS: DTI values at T0 were generally poor predictors of outcome at 1 year, whereas Loes scores were generally good predictors. MD within the optic radiations strongly correlates with NFS over that year. In addition, certain normal-appearing regions, such as cerebellar WM, may have DTI abnormalities before HSCT that persist after HSCT

Effect of Patient Positioning on Cerebrospinal Fluid Opening Pressure

Background: Prone is the preferred patient position for fluoroscopic-guided lumbar puncture (LP). Normative data for cerebrospinal fluid (CSF) opening pressure (OP) exist for lateral decubitus (LD) positioning only and have not been defined for the prone position. This study compares CSF OP values in the prone and LD positions and examines the effect of body mass index (BMI) on OP. Methods: Patients undergoing diagnostic or therapeutic fluoroscopic-guided LP were recruited prospectively at 2 tertiary care centers from 2009 to 2012. Following prone fluoroscopic-guided LP, patients were rolled to the LD position for repeat CSF OP measurement. In addition to comparing the mean OP in each position, the relationships between OP, body position, and BMI were also explored. Results: Fifty-two patients were enrolled. A mean OP difference of 1.2 cm H2O was observed (prone: 26.5 cm H2O; LD: 27.7 cm H2O; P = 0.07). No correlation between CSF OP and BMI was seen in either position. Conclusions: No statistically or clinically significant difference between prone and LD OP was identified. BMI does not appear to affect CSF OP measurement in either position. (C) 2014 by North American Neuro-Ophthalmology Societ

Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy

Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in ABCD1, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention