The cerebellar (para)flocculus:A review on its auditory function and a possible role in tinnitus

The cerebellum is historically considered to be involved in motor control and motor learning. However, it is also a site of multimodal sensory and sensory-motor integration, implicated in auditory processing. The flocculus and paraflocculus are small lobes of the cerebellum, in humans located in the cerebellopontine angle. The last two decades, both structures have been a subject of interest in hearing loss and tinnitus research. The current review summarizes insights on the auditory function of the (para)flocculus and its contribution to hearing loss and tinnitus. This leads to the hypothesis of a feedback loop between the paraflocculus and the auditory cortex. Disruption of this loop may be instrumental in both maintaining tinnitus and reducing tinnitus. Although the research mostly has been performed in animals, the implications in humans are also discussed. If the (para)flocculus indeed comprises an auditory function and is part of a tinnitus-mechanism, this would potentially open up new treatment options that involve direct intervention at the (para)flocculus

The Role of Inflammation in Tinnitus:A Systematic Review and Meta-Analysis

Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In this systematic review, the role of inflammation in subjective tinnitus was studied. Nine animal and twenty human studies reporting inflammatory markers in both humans and animals with tinnitus were included. It was established that TNF-α and IL-1β are increased in tinnitus, and that microglia and astrocytes are activated as well. Moreover, platelet activation may also play a role in tinnitus. In addition, we elaborate on mechanisms of inflammation in tinnitus, and discuss potential treatment options targeting inflammatory pathways

Cerebellar Gray Matter Volume in Tinnitus

Tinnitus is the perception of sound without an external source. The flocculus (FL) and paraflocculus (PFL), which are small lobules of the cerebellum, have recently been implicated in its pathophysiology. In a previous study, the volume of the (P)FL-complex correlated with tinnitus severity in patients that had undergone cerebellopontine angle (CPA) tumor removal. In this study, the relation between tinnitus and gray matter volume (GMV) of the (P)FL-complex, GMV of the other cerebellar lobules and GMV of the cerebellar nuclei is investigated in otherwise healthy participants. Data was processed using the SUIT toolbox, which is dedicated to analysis of imaging data of the human cerebellum. GMV of all cerebellar lobules and nuclei were similar between tinnitus and non-tinnitus participants. Moreover, no relation was present between tinnitus severity, as measured by the Tinnitus Handicap Inventory, and (P)FL-complex GMV, tonsil GMV, or total cerebellar cortical GMV. These results suggest that in otherwise healthy participants, in contrast to participants after CPA tumor removal, no relation between the GMV of neither the (P)FL-complex nor other cerebellar lobules and tinnitus presence and severity exists. These findings indicate that a relation only exists when the (P)FL-complex is damaged, for instance by a CPA tumor. Alternatively, it is possible that differences in (P)FL-complex GMVs are too small to detect with a voxel-based morphometry study. Therefore, the role of the (P)FL-complex in tinnitus remains to be further studied

Accurate assessment of abdominal aortic aneurysm with intravascular ultrasound scanning: Validation with computed tomographic angiography

AbstractPurpose: The purpose of this study was to assess the accuracy of intravascular ultrasound (IVUS) parameters of abdominal aortic aneurysm, used for endovascular grafting, in comparison with computed tomographic angiography (CTA). Methods: This study was designed as a descriptive study. Between March 1997 and March 1998, 16 patients with abdominal aortic aneurysms were studied with angiography, IVUS (12.5 MHz), and CTA. The length of the aneurysm and the length and lumen diameter of the proximal and distal neck obtained with IVUS were compared with the data obtained with CTA. The measurements with IVUS were repeated by a second observer to assess the reproducibility. Tomographic IVUS images were reconstructed into a longitudinal format. Results: IVUS results identified 31 of 32 renal arteries and four of five accessory renal arteries. A comparison of the length measurements of the aneurysm and the proximal and distal neck obtained with IVUS and CTA revealed a correlation of 0.99 (P < .001), with a coefficient of variation of 9%. IVUS results tended to underestimate the length as compared with the CTA results (0.48 ± 0.52 cm; P < .001). A comparison of the lumen diameter measurements of the proximal and distal neck derived from IVUS and CTA showed a correlation of 0.93 (P < .001), with a coefficient of variation of 9%. IVUS results tended to underestimate aneurysm neck diameter as compared with CTA results (0.68 ± 1.76 mm; P = .006). Interobserver agreement of IVUS length and diameter measurements showed a good correlation (r = 1.0; P < .001), with coefficients of variation of 3% and 2%, respectively, and no significant differences (0.0 ± 0.16 cm and 0.06 ± 0.36 mm, respectively). The longitudinal IVUS images displayed the important vascular structures and improved the spatial insight in aneurysmal anatomy. Conclusion: Intravascular ultrasound scanning results provided accurate and reproducible measurements of abdominal aortic aneurysm. The longitudinal reconstruction of IVUS images provided additional knowledge on the anatomy of the aneurysm and its proximal and distal neck. (J Vasc Surg 1999;29:631-8.

Endovascular repair versus open surgery in patients with ruptured abdominal aortic aneurysms: Clinical outcomes with 1-year follow-up

ObjectiveTo compare the clinical outcomes of treatment after endovascular repair and open surgery in patients with ruptured infrarenal abdominal aortic aneurysms (AAAs), including 1-year follow-up.MethodsAll consecutive conscious patients with ruptured infrarenal AAAs who presented to our tertiary care teaching hospital between January 1, 2001, and December 31, 2005, were included in this study (n = 55). Twenty-six patients underwent endovascular repair, and 29 patients underwent open surgery. Patients who were hemodynamically too unstable to undergo a computed tomography angiography scan were excluded. Outcomes evaluated were intraoperative mortality, 30-day mortality, systemic complications, complications necessitating surgical intervention, and mortality and complications during 1-year follow-up. The statistical tests we used were the Student t test, χ2 test, Fisher exact test, and Mann-Whitney U test (two sided; α = .05).ResultsThirty-day mortality was 8 (31%) of 26 patients who underwent endovascular repair and 9 (31%) of 29 patients who underwent open surgery (P = .98). Systemic complications and complications necessitating surgical intervention during the initial hospital stay were similar in both treatment groups (8/26 [31%] and 5/26 [19%] for endovascular repair, respectively, and 9/29 [31%] and 8/29 [28%] for open surgery, respectively; P > .40). During 1-year follow-up, two patients initially treated with endovascular repair died as a result of non–aneurysm-related causes; no death occurred in the open surgery group. Complications during 1-year follow-up were 1 (5%) of 20 for endovascular repair and 4 (16%) of 25 for open surgery (P = .36).ConclusionsOn the basis of our study with a highly selected population, the mortality and complication rates after endovascular repair may be similar compared with those after open surgery in patients treated for ruptured infrarenal AAAs

Bilateral Pallidotomy for Dystonia:A Systematic Review

Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations

INTRODUCTION: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity. METHODS: The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies. RESULTS: Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4. CONCLUSION: Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation

Surgical clipping as the preferred treatment for aneurysms of the middle cerebral artery

In recent years the endovascular treatment of intracranial aneurysms (coiling) has progressively gained recognition, particularly after the publication of the International Subarachnoid Aneurysm Trial (ISAT) in 2002. Despite the fact that in ISAT middle cerebral artery (MCA) aneurysms were clearly underrepresented, the study is often used as an argument to favor coiling above surgery in MCA aneurysms. Taken into account that MCA aneurysms are very well accessible for surgery, a contemporary assessment of the benefits of a preferred surgical strategy for MCA aneurysms was performed in a tertiary neurovascular referral center. A prospectively kept single-center database of 151 consecutive patients with an MCA aneurysm was reviewed over a 6-year period (2001-2006). Long-term follow-up after surgical treatment of a ruptured MCA aneurysm was obtained in 74 out of 77 (96%) patients. The outcome was compared with relevant series in the literature. After a mean follow-up of 4.7 years, 59 out of 74 surgically treated patients (80%) with a ruptured MCA aneurysm had a good outcome (mRankin 0-2). All patients with an unruptured MCA aneurysm also had a good outcome after clipping. This is well-matched with the findings of the literature search, and competitive with the endovascular results. Surgical clipping is recommended as the principal treatment strategy for MCA aneurysms. This is not only ethically defendable in view of the surgical results but also in line with a strategy to maintain surgical experience within centralized neurovascular centers

Fluorescence-guided detection of pituitary neuroendocrine tumor (PitNET) tissue during endoscopic transsphenoidal surgery available agents, their potential, and technical aspects

Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future

The Unruptured Intracranial Aneurysm Treatment Score as a Predictor of Aneurysm Growth or Rupture

Background and purpose: The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was built to harmonize the treatment decision making on unruptured intracranial aneurysms. Therefore, it may also function as a predictor of aneurysm progression. In this study, we aimed to assess the validity of the UIATS model to identify aneurysms at risk of growth or rupture during follow-up. Methods: We calculated the UIATS for a consecutive series of conservatively treated unruptured intracranial aneurysms, included in our prospectively kept neurovascular database. Computed tomography angiography and/or magnetic resonance angiography imaging at baseline and during follow-up was analyzed to detect aneurysm growth. We defined rupture as a cerebrospinal fluid or computed tomography-proven subarachnoid hemorrhage. We calculated the area under the receiver operator curve, sensitivity, and specificity, to determine the performance of the UIATS model. Results: We included 214 consecutive patients with 277 unruptured intracranial aneurysms. Aneurysms were followed for a median period of 1.3 years (range 0.3-11.7 years). During follow-up, 17 aneurysms enlarged (6.1%), and two aneurysms ruptured (0.7%). The UIATS model showed a sensitivity of 80% and a specificity of 44%. The area under the receiver operator curve was 0.62 (95% confidence interval 0.46-0.79). Conclusions: Our observational study involving consecutive patients with an unruptured intracranial aneurysm showed poor performance of the UIATS model to predict aneurysm growth or rupture during follow-up