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

Intracranial aneurysm wall enhancement as an indicator of instability:a systematic review and meta-analysis

BACKGROUND AND PURPOSE: Aneurysm wall enhancement (AWE) of intracranial aneurysms on magnetic resonance imaging has been described in previous studies as a surrogate marker of instability. With this study, an updated literature overview and summary risk estimates of the association between AWE and different specific outcomes (i.e., rupture, growth or symptomatic presentation) for both cross-sectional and longitudinal studies are provided. METHODS: The PRISMA guideline was followed and a search was performed of PubMed and Embase to 1 January 2021 for studies that reported on AWE and aneurysm instability. In cross-sectional studies, AWE was compared between patients with stable and unstable aneurysms. In longitudinal studies, AWE of stable aneurysms was assessed at baseline after which patients were followed longitudinally. Risk ratios were calculated for longitudinal studies, prevalence ratios for cross-sectional studies and then the ratios were pooled in a random-effects meta-analysis. Also, the performance of AWE to differentiate between stable and unstable aneurysms was evaluated. RESULTS: Twelve studies were included with a total of 1761 aneurysms. In cross-sectional studies, AWE was positively associated with rupture (prevalence ratio 11.47, 95% confidence interval [CI] 4.05-32.46) and growth or symptomatic presentation (prevalence ratio 4.62, 95% CI 2.85-7.49). Longitudinal studies demonstrated a positive association between AWE and growth or rupture (risk ratio 8.00, 95% CI 2.14-29.88). Assessment of the performance of AWE showed high sensitivities, mixed specificities, low positive predictive values and high negative predictive values. CONCLUSIONS: Although AWE is positively associated with aneurysm instability, current evidence mostly supports the use of its absence as a surrogate marker of aneurysm stability

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

Spinal Cord Ischemia Related to Disc Herniation:Case Report and a Review of the Literature

Symptoms of spinal cord ischemia can mimic myelopathy due to spinal cord compression in the acute phase. Thoracic disc herniation with limited spinal cord compression but rapid progression of neurological symptoms causes a clinical dilemma as to whether emergency decompression should be performed. We report a case of acute progressive myelopathy due to spinal cord ischemia related to thoracic disc herniation initially managed by Th8 laminectomy with reduction of the herniated disc. Repeat imaging showed T2-weighted hyperintensity in the posterior cord. The clinical and radiological course supports posterior spinal artery ischemia. This case illustrates and a review of the literature shows that thoracic disc herniation may be complicated by ischemic myelopathy even in the absence of cord compression

An Unusual Triad in Pediatric Neurology:A Case Report on Cerebral Palsy, Epilepsy, and Duchenne Muscular Dystrophy

We present a case of an unusual triad in pediatric neurology: a currently 12-year-old boy with cerebral palsy and epilepsy who was later also diagnosed with Duchenne muscular dystrophy. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different neurological disorders may overshadow each other. In addition, it demonstrates that every child with cerebral palsy and either an atypical clinical course or with inexplicable laboratory values-as well as every infant boy born to a theoretical Duchenne muscular dystrophy carrier-should be subjected to additional investigations.</p

Dystrophin Distribution and Expression in Human and Experimental Temporal Lobe Epilepsy

Objective: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE). Method: Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats. Results: Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p < 0.05), whereas the level of the shorter Dp71 isoform did not differ. In contrast, AK animals showed similar dystrophin levels as controls. Conclusion: Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated in human TLE, but not in AK rats, possibly indicating a compensatory mechanism in the chronic epileptic human brain

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

Augmented reality—The way forward in patient education for intracranial aneurysms? A qualitative exploration of views, expectations and preferences of patients suffering from an unruptured intracranial aneurysm regarding augmented reality in patient education

Objectives: The goal of this project is to explore the views, expectations and preferences of patients with an unruptured intracranial aneurysm regarding the use of AR in patient education.Methods: To gain an in-depth understanding of the patients’ perspective, a face-to-face interview study was conducted using an interview protocol with a predefined topic list. All interviews were audio-recorded and transcribed verbatim afterwards. Transcripts were analyzed using thematic content analyses. Coding was performed using Atlas.ti software.Results: Seventeen interviews were conducted. The views, expectations and preferences of patients regarding patient education with AR could be subdivided into 15 categories, which could be grouped into 4 general themes: 1) experiences with current patient education, 2) expectations of AR in patient education, 3) opportunities and limitations of AR, and 4) out-of-hospital use of an AR application. Patients’ expectations were predominantly positive regarding improving patients’ understanding of their medical situation and doctor-patient communication.Discusssion: This study suggests that patients with unruptured intracranial aneurysms are open to receive patient education regarding their disease with AR. Patients expect that AR models can help patients with intra-cranial aneurysms better understand their disease, treatment options and risks. Additionally, patients expect AR could improve doctor-patient communication

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms An Individual Patient Data Meta-analysis

OBJECTIVE: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIA) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis we performed an Embase and Pubmed search for studies published up to December 1, 2020. We included studies that 1) had a prospective study design; 2) included 50 or more patients with UIA; 3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and 4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial versus sporadic UIA using a Cox proportional hazard regression model adjusted for the PHASES score and smoking. We performed two analyses: 1. only studies defining first-degree relatives as parents, children, and siblings and 2. all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from eight cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings and children in six cohorts (29% Dutch, 55% Finnish, 15% Japanese), totalling 2,297 patients (17% familial, 399 patients) with 3,089 UIA and 7,301 person-years follow-up. Rupture occurred in 10 familial patients (rupture rate: 0·89%/person-year; 95% CI:0·45-1·59) and 41 sporadic patients (0·66%/person-year; 95% CI:0·48-0·89); adjusted HR for familial patients 2·56 (95% CI: 1·18-5·56). After adding also the two cohorts excluding siblings as first-degree relatives resulting in 9,511 patients the adjusted HR was 1·44 (95% CI: 0·86-2·40). CONCLUSION: The risk of rupture of UIA is two and a half times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account

Sex Difference and Rupture Rate of Intracranial Aneurysms : An Individual Patient Data Meta-Analysis

Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (>= 7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.Peer reviewe