Cerebrospinal fluid-lymphatic fistula in a child with generalized lymphatic anomaly treated with targeted blood patch - a rare case report and review of the literature.

Spontaneous intracranial hypotension may result in debilitating postural headaches and severe neurological symptoms due to secondary cerebellar sagging. The most common cause is the cerebrospinal fluid (CSF) leak within the spinal canal. Although previously reported in only a few cases, also paraspinal lymphatic malformations causing vertebral bone destruction may occasionally result in CSF leak to these pathological formations. Here, we present a case of a 9-year-old girl with generalized lymphatic anomaly (GLA) presenting with severe postural headache. Radiological imaging revealed a typical feature of cerebellar sagging. Myelography localized the CSF leakage into vertebral bodies of C7 and Th1, which both were partly involved in pathological paravertebral masses of known lymphatic anomaly, and from there along the right C8 nerve root sleeve into the anomaly. As the C8-nerve root could not be ligated due to the risk of significant neurological injury, we attempted image-guided targeted percutaneous epidural placement of a blood patch directly into the foramen at the affected level. The procedure resulted in obliteration of the fistula and regression of cerebellar sagging, with significant relief of symptoms. Although it is an extremely rare coincidence, patients with paraspinal lymphatic malformations may develop intraspinal CSF leak into these pathological formations. The present case report suggests that besides a direct surgical obliteration of the fistula and sacrificing the nerve root, a targeted percutaneous epidural blood patch may be a possible alternative in the case of a functionally important nerve root.

Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease, characterized by cerebrospinal fluid (CSF) flow disturbance. Today, the only available treatment is CSF diversion surgery (shunt surgery). While traditional imaging biomarkers typically assess CSF space anatomy, recently introduced imaging biomarkers of CSF dynamics and glymphatic enhancement, provide imaging of CSF dynamics and thereby more specifically reveal elements of the underlying pathophysiology. The biomarkers address CSF ventricular reflux grade as well as glymphatic enhancement and derive from intrathecal contrast-enhanced MRI. However, the contrast agent serving as CSF tracer is administered off-label. In medicine, the introduction of new diagnostic or therapeutic methods must consider the balance between risk and benefit. To this end, we performed a prospective observational study of 95 patients with iNPH, comparing different intrathecal doses of the MRI contrast agent gadobutrol (0.10, 0.25, and 0.50 mmol, respectively), aiming at the lowest reasonable dose needed to retrieve diagnostic information about the novel MRI biomarkers. The present observations disclosed a dose-dependent enrichment of subarachnoid CSF spaces (cisterna magna, vertex, and velum interpositum) with dose-dependent ventricular reflux of tracer in iNPH, as well as dose-dependent glymphatic tracer enrichment. The association between tracer enrichment in CSF and parenchymal compartments were as well dose-related. Intrathecal gadobutrol in a dose of 0.25 mmol, but not 0.10 mmol, was at 1.5T MRI considered sufficient for imaging altered CSF dynamics and glymphatic enhancement in iNPH, even though 3T MRI provided better sensitivity. Tracer enrichment in CSF at the vertex and within the cerebral cortex and subcortical white matter was deemed too low for maintaining diagnostic information from a dose of 0.10 mmol. We conclude that reducing the intrathecal dose of gadobutrol from 0.50 to 0.25 mmol gadobutrol improves the safety margin while maintaining the necessary diagnostic information about disturbed CSF homeostasis and glymphatic failure in iNPH.

Off-label intrathecal use of gadobutrol: safety study and comparison of administration protocols.

PURPOSE: Magnetic resonance imaging (MRI) contrast agents have been used off-label for diagnosis of cerebrospinal fluid (CSF) leaks and lately also for assessment of the glymphatic system and meningeal lymphatic drainage. The purpose of this study was to further evaluate the short- and long-term safety profile of intrathecal MRI contrast agents. METHODS: In this prospective study, we compared the safety profile of different administration protocols of intrathecal gadobutrol (GadovistTM; 1.0 mmol/ml). Gadobutrol was administered intrathecal in a dose of 0.5 mmol, with or without iodixanol (VisipaqueTM 270 mg I/ml; 3 ml). In addition, a subgroup was given intrathecal gadobutrol in a dose of 0.25 mmol. Adverse events were assessed at 1 to 3 days, 4 weeks, and after 12 months. RESULTS: Among the 149 patients, no serious adverse events were seen in patients without history of prior adverse events. The combination of gadobutrol with iodixanol did not increase the occurrence of non-serious adverse events after days 1-3. Intrathecal gadobutrol in a dose of 0.25 mmol caused less severity of nausea, as compared with the dose of 0.5 mmol. The clinical diagnosis was the major determinant for occurrence of non-serious adverse events after intrathecal gadobutrol. CONCLUSION: This prospective study showed that intrathecal administration of gadobutrol in a dose of 0.5 mmol is safe. Non-serious adverse events were to a lesser degree affected by the administration protocols, though preliminary data are given that side effects of intrathecal gadobutrol are dose-dependent.

Fat in the lumbar multifidus muscles - predictive value and change following disc prosthesis surgery and multidisciplinary rehabilitation in patients with chronic low back pain and degenerative disc: 2-year follow-up of a randomized trial.

BACKGROUND: Evidence is lacking on whether fat infiltration in the multifidus muscles affects outcomes after total disc replacement (TDR) surgery and if it develops after surgery. The aims of this study were 1) to investigate whether pre-treatment multifidus muscle fat infiltration predicts outcome 2 years after treatment with TDR surgery or multidisciplinary rehabilitation, and 2) to compare changes in multifidus muscle fat infiltration from pre-treatment to 2-year follow-up between the two treatment groups. METHODS: The study is secondary analysis of data from a trial with 2-year follow-up of patients with chronic low back pain (LBP) and degenerative disc randomized to TDR surgery or multidisciplinary rehabilitation. We analyzed (aim 1) patients with both magnetic resonance imaging (MRI) at pre-treatment and valid data on outcome measures at 2-year follow-up (predictor analysis), and (aim 2) patients with MRI at both pre-treatment and 2-year follow-up. Outcome measures were visual analogue scale (VAS) for LBP, Oswestry Disability Index (ODI), work status and muscle fat infiltration on MRI. Patients with pre-treatment MRI and 2-year outcome data on VAS for LBP (n = 144), ODI (n = 147), and work status (n = 137) were analyzed for prediction purposes. At 2-year follow-up, 126 patients had another MRI scan, and change in muscle fat infiltration was compared between the two treatment groups. Three radiologists visually quantified multifidus muscle fat in the three lower lumbar levels on MRI as <20% (grade 0), 20-50% (grade 1), or >50% (grade 2) of the muscle cross-section containing fat. Regression analysis and a mid-P exact test were carried out. RESULTS: Grade 0 pre-treatment multifidus muscle fat predicted better clinical results at 2-year follow-up after TDR surgery (all outcomes) but not after rehabilitation. At 2-year follow-up, increased fat infiltration was more common in the surgery group (intention-to-treat p = 0.03, per protocol p = 0.08) where it was related to worse pain and ODI. CONCLUSIONS: Patients with less fat infiltration of multifidus muscles before TDR surgery had better outcomes at 2-year follow-up, but findings also indicated a negative influence of TDR surgery on back muscle morphology in some patients. The rehabilitation group maintained their muscular morphology and were unaffected by pre-treatment multifidus muscle fat. TRIAL REGISTRATION: NCT 00394732 (retrospectively registered October 31, 2006).

Cerebral Aneurysm Morphology Before and After Rupture: Nationwide Case Series of 29 Aneurysms.

BACKGROUND AND PURPOSE: Using postrupture morphology to predict rupture risk of an intracranial aneurysm may be inaccurate because of possible morphological changes at or around the time of rupture. The present study aims at comparing morphology from angiograms obtained prior to and just after rupture and to evaluate whether postrupture morphology is an adequate surrogate for rupture risk. METHODS: Case series of 29 aneurysms from a nationwide retrospective data collection. Two neuroradiologists who were blinded to pre- versus postrupture images assessed predefined morphological parameters independently and reached consensus regarding all measurements. Prerupture morphology and respective changes after rupture were quantified and linked to risk factors and to the risk of rupture according to the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, site of aneurysm) and unruptured intracranial aneurysm treatment (UIAT) scores. RESULTS: All 1-dimensional parameter medians were significantly larger after rupture, except neck diameter. Number of aneurysms with daughter sacs was 9 (31%) before and 17 (59%) after rupture (P=0.005). Aneurysm growth from the images prior to and just after rupture increased with the time elapsed between images. Aneurysms in patients with hypertension were significantly larger at diagnosis. Prerupture morphology did not differ in relation to smoke status. Clinical risk factors were not significantly associated with morphological change. CONCLUSIONS: The changes in aneurysm morphology observed after rupture reflect the compound effect of time with successive growth and formation of irregularities and the impact of rupture per se. Postrupture morphology should not be considered an adequate surrogate for the prerupture morphology in the evaluation of rupture risk.

Age-related differences in brain network activation and co-activation during multiple object tracking.

INTRODUCTION: Multiple object tracking (MOT) is a powerful paradigm for measuring sustained attention. Although previous fMRI studies have delineated the brain activation patterns associated with tracking and documented reduced tracking performance in aging, age-related effects on brain activation during MOT have not been characterized. In particular, it is unclear if the task-related activation of different brain networks is correlated, and also if this coordination between activations within brain networks shows differential effects of age. METHODS: We obtained fMRI data during MOT at two load conditions from a group of younger (n = 25, mean age = 24.4 ± 5.1 years) and older (n = 21, mean age = 64.7 ± 7.4 years) healthy adults. Using a combination of voxel-wise and independent component analysis, we investigated age-related differences in the brain network activation. In order to explore to which degree activation of the various brain networks reflect unique and common mechanisms, we assessed the correlations between the brain networks' activations. RESULTS: Behavioral performance revealed an age-related reduction in MOT accuracy. Voxel and brain network level analyses converged on decreased load-dependent activations of the dorsal attention network (DAN) and decreased load-dependent deactivations of the default mode networks (DMN) in the old group. Lastly, we found stronger correlations in the task-related activations within DAN and within DMN components for younger adults, and stronger correlations between DAN and DMN components for older adults. CONCLUSION: Using MOT as means for measuring attentional performance, we have demonstrated an age-related attentional decline. Network-level analysis revealed age-related alterations in network recruitment consisting of diminished activations of DAN and diminished deactivations of DMN in older relative to younger adults. We found stronger correlations within DMN and within DAN components for younger adults and stronger correlations between DAN and DMN components for older adults, indicating age-related alterations in the coordinated network-level activation during attentional processing.

Do more MRI findings imply worse disability or more intense low back pain? A cross-sectional study of candidates for lumbar disc prosthesis.

OBJECTIVE: To examine whether combined magnetic resonance imaging (MRI) findings are related to the degree of disability and low back pain (LBP) in candidates for lumbar disc prosthesis surgery. MATERIALS AND METHODS: This cross-sectional study included 170 disc prosthesis candidates (mean age 41 years; 88 women) with chronic non-radicular LBP and localized disc degeneration. Experienced radiologists rated Modic changes and disc findings at L4-S1 on pre-treatment MRIs. An MRI total score (0-10) for findings at L4/L5 plus L5/S1 was calculated for Modic type I and/or II changes, a posterior high intensity zone (HIZ) in the disc, dark/black nucleus pulposus signal, and ≥40 % disc height decrease. We analyzed the relationship of the MRI total score to the Oswestry Disability Index (ODI) (n = 170) and LBP intensity scores (0-100 visual analogue scale, n = 165) using multiple linear regression and adjusting for age, gender, body mass index, smoking, and anxiety/depression. RESULTS: The MRI total score was not related to ODI (regression coefficient 0.12, p = 0.79) or LBP intensity (regression coefficient 0.64, p = 0.37). When individual MRI findings were analyzed, patients with HIZ at L5/S1 had slightly lower ODI scores (4.7 points, p = 0.02). In post hoc analyses, results remained unchanged after adding facet arthropathy to the MRI total score and adjusting also for physical workload and physical leisure-time activity. CONCLUSIONS: The combined MRI findings were not related to the degree of disability or the intensity of LBP. These degenerative MRI findings cannot explain variation in pre-treatment disability and pain in patients with chronic LBP accepted for disc prosthesis surgery.

Adjacent level degeneration and facet arthropathy after disc prosthesis surgery or rehabilitation in patients with chronic low back pain and degenerative disc: second report of a randomized study.

STUDY DESIGN: Randomized clinical trial with 2-year follow-up. OBJECTIVE: To assess the development of adjacent level degeneration (ALD) and index level facet arthropathy (FA) in patients treated with disc prosthesis compared with patients treated with rehabilitation. SUMMARY OF BACKGROUND DATA: There is controversy about the natural history of disc degeneration and the development of ALD and FA in patients who undergo disc prosthesis surgery. METHODS: The study included 116 patients with a history of low back pain for at least 1 year, Oswestry Disability Index 30 points or more, and degenerative changes in 1 or 2 lower lumbar spine levels. Magnetic resonance imaging was performed before treatment and at the 2-year follow-up. ALD and index level FA were determined on the basis of the majority assessment of 3, independent, experienced radiologists. ALD was assessed by evaluating Modic changes, posterior high intensity zone in the disc, nucleus pulposus signal, disc height, disc contour, and FA. Data were analyzed with Fischer exact test and t test. RESULTS: ALD developed with similar frequencies in patients who were (n = 59) and were not (n = 57) treated with surgery. In patients treated with surgery, index level FA appeared or increased in 20 patients (34%) and decreased in 1 patient. In patients treated with rehabilitation, 2 (4%) had new or increased FA at the index/degenerated disc level and 1 had decreased FA (P < 0.001). The development of ALD and FA was not related to clinical outcome. CONCLUSION: In this first study that compared the courses of degeneration after treatment with disc prosthesis surgery or rehabilitation, ALD was observed at similar frequencies at the 2-year follow-up. However, the surgery group had increased FA at the implant level.

Reliability of change in lumbar MRI findings over time in patients with and without disc prosthesis--comparing two different image evaluation methods.

OBJECTIVES: To assess the reliability of change in lumbar magnetic resonance imaging (MRI) findings evaluated retrospectively by direct comparison of images and by non-comparison. MATERIALS AND METHODS: Pre-treatment and 2-year follow-up MRI was performed in 126 patients randomized to disc prosthesis surgery or non-surgical treatment. Two experienced radiologists independently evaluated progress and regress for Modic changes, disc findings, and facet arthropathy (FA) at L3/L4, L4/L5, and L5/S1, both by non-comparison and by comparison of initial and follow-up images. FA was evaluated at all levels, and other findings at non-operated levels. We calculated prevalence- and bias-adjusted kappa (PABAK) values for interobserver agreement. The impact of an adjacent prosthesis (which causes artefacts) and image evaluation method on PABAK was assessed using generalized estimating equations. RESULTS: Image comparison indicated good interobserver agreement on progress and regress (PABAK 0.63-1.00) for Modic changes, posterior high-intensity zone, disc height, and disc contour at L3-S1 and for nucleus pulposus signal and FA at L3/L4; and moderate interobserver agreement (PABAK 0.46-0.59) on decreasing nucleus signal and increasing FA at L4-S1. Image comparison indicated lower (but fair) interobserver agreement (PABAK 0.29) only for increasing FA at L5/S1 in patients with prosthesis in L4/L5 and/or L5/S1. An adjacent prosthesis had no overall impact on PABAK values (p ≥ 0.22). Comparison yielded higher PABAK values than non-comparison (p < 0.001). CONCLUSIONS: Regarding changes in lumbar MRI findings over time, comparison of images can provide moderate or good interobserver agreement, and better agreement than non-comparison. An adjacent prosthesis may not reduce agreement on change for most findings.

Reliability of MRI findings in candidates for lumbar disc prosthesis.

INTRODUCTION: Limited reliability data exist for localised magnetic resonance imaging (MRI) findings relevant to planning of treatment with lumbar disc prosthesis and later outcomes. We assessed the reliability of such findings in chronic low back pain patients who were accepted candidates for disc prosthesis. METHODS: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three experienced radiologists independently rated Modic changes, disc findings and facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126 examinations. For each MRI finding at each disc level, agreement was analysed using the kappa statistic and differences in prevalence across observers using a fixed effects model. RESULTS: All findings at L3/L4 and facet arthropathy at L5/S1 had a mean prevalence <10% across observers and were not further analysed, ensuring interpretable kappa values. Overall interobserver agreement was generally moderate or good (kappa 0.40-0.77) at L4-S1 for Modic changes, nucleus pulposus signal, disc height (subjective and measured), posterior high-intensity zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height at L4/L5 differed up to threefold in prevalence between observers (p < 0.0001). Intraobserver agreement was mostly good or very good (kappa 0.60-1.00). CONCLUSION: In candidates for disc prosthesis, mostly moderate interobserver agreement is expected for localised MRI findings.

Magnetic resonance imaging of ligaments and membranes in the craniocervical junction in whiplash-associated injury and in healthy control subjects.

BACKGROUND: The pathogenesis and imaging findings in whiplash-associated injury (WAD) are poorly understood and remain debatable. PURPOSE: To assess the ligaments and membranes in the craniocervical junction with magnetic resonance imaging (MRI) in patients with WAD and to compare them with healthy control subjects. MATERIAL AND METHODS: Twenty-eight patients with WAD were selected at random from a total number of 180 examined with MRI using 2-mm proton density (PD)-weighted images in three orthogonal planes at 1.5T. The patients were compared with 27 healthy control subjects without neck trauma. RESULTS: High signal intensity of the alar and transverse ligaments was quite common and was reported at an average of about 50% both among patients and control subjects. The incidence of abnormalities of the tectorial and posterior atlantooccipital membranes was low in both groups. No statistically significant difference between control subjects and patients with WAD was revealed for any of the structures assessed. Additional fat-suppressed images seemed to reduce the number of reported anomalies. CONCLUSION: Due to lack of significant differences between patients with WAD and healthy control subjects, it is not recommended that MRI with the current technique and classification system be used in the routine workup of patients with WAD.