Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease.

Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1ß into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64 × 10-6) and IGLV3-21 (p = 6.28 × 10-3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1ß with up-regulation of IL6 (p = 7.65 × 10-8) and INHBA (p = 3.39 × 10-7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.

Vestibular Hypofunction Secondary to Topical Use of Aminoglycosides in ears with perforated tympanic membrane.

INTRODUCTION: The objective of this study was to identify and clinically characterize patients treated in an Otoneurology Unit who experienced vestibular ototoxicity as a result of using aminoglycoside ear drops during outbreaks of superinfection in chronic otitis media. MATERIAL AND METHODS: An observational retrospective study was conducted, including patients with perforated eardrums who developed vestibular ototoxicity within the past ten years following the application of topical ear aminoglycosides in a tertiary referral center. The study encompassed the assessment of the clinical presentation, treatment, quality of life, and evolution after treatment of the identified individuals. RESULTS: During the study period, six patients, aged between 33 and 71 years, developed vestibular ototoxicity following the use of topical aminoglycoside drops due infection flares in chronic otitis media. All cases involved the use of gentamicin. Two cases were unilateral, and four were unilateral. The onset of symptoms occurred within one to four weeks of using the drops, resulting in all patients experiencing instability without vertigo attacks. After discontinuing the drops and undergoing vestibular rehabilitation, four patients experienced sequelae, with two patients (both with bilateral vestibular hypofunction) suffering significant impairment in their quality of life. CONCLUSIONS: Conclusion: Vestibular ototoxicity due to the topical application of aminoglycosides during acute exacerbations of chronic otitis media is a rare occurrence. However, given its potential for severe consequences and the fact that we are still encountering patients with this condition, healthcare professionals should explore alternative antibacterial agents that offer similar efficacy.

Sudden hearing loss secondary to syphilis.

BACKGROUND: Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum, whose incidence has increased significantly in recent years. Some patients may develop sudden hearing loss (SHL) against the background of otosyphilis. OBJECTIVES: The objective of our study was to determine whether routine lues serology is useful in patients presenting with sudden hearing loss. METHODS: For this purpose, all cases of SHL treated in our hospital during a period of 6 years were propectively collected. The frequency of positivity for syphilis in these patients, the treatment received, and their evolution were determined. RESULTS: Of the total number of patients evaluated during that period, 71 underwent serological screening for syphilis, of whom 2 (2.8 %) presented positive screening antibodies. In one of them, the RPR was normal and had been treated with lues a few years before. After treatment there was no improvement. The other patient, diagnosed with otosyphilis with unconfirmed suspected neurological disease, showed normalization of hearing after specific treatment. CONCLUSIONS: Since it is a potentially curable disease, despite the low overall frequency of syphilis in patients with SHL it is advisable to perform serological screening for syphilis in high risk patients (e.g., incarceration, multiple recent sexual partners, men who have sex with men) or atypical clinical presentation (e.g., concurrent neuropathies).

A Predictive Model of Bilateral Sensorineural Hearing Loss in Meniere Disease Using Clinical Data.

OBJECTIVES: Meniere disease (MD) is defined by a clinical syndrome of recurrent attacks of spontaneous vertigo associated with tinnitus, aural fullness, and sensorineural hearing loss (SNHL). Most patients have unilateral SNHL, but some of them will develop contralateral SNHL during the course of the disease. Several studies have reported a frequency of 2 to 73% SNHL in the second ear, according to the duration of disease and the period of follow-up. We hypothesize that unilateral and bilateral MD are different conditions, the first would initially involve the apical turn of the cochlea, while bilateral MD would affect the entire length of the cochlea. The aim of the study is to search for clinical predictors of bilateral SNHL in MD to build a predictive model of bilateral involvement. DESIGN: A retrospective, longitudinal study including two cohorts with a total of 400 patients with definite MD was carried out. The inception cohort consisted of 150 patients with MD and the validation cohort included 250 cases. All of the cases were diagnosed of unilateral MD according to their hearing loss thresholds. The following variables were assessed as predictors of bilateral SNHL for the two cohorts: sex, age of onset, familiar history of MD, migraine and high-frequency hearing loss (HFHL, defined if hearing threshold >20 dB in two or more consecutive frequencies from 2 to 8 KHz). A descriptive analysis was carried out according to the presence of HFHL in the first audiogram for the main variables. By using multiple logistic regression, we built-up several predictive models for the inception cohort and validated it with the replication cohort and merged dataset. RESULTS: Twenty-three (19.3%) and 78 (41%) of patients with HFHL developed contralateral SNHL during the follow-up, in the inception and validation cohorts, respectively. In the inception cohort, the best predictive model included HFHL in the first audiogram (OR = 6.985, p = 0.063) and the absence of migraine (OR = 0.215, p = 0.144) as clinical predictors for bilateral SNHL [area under the curve (AUC) = 0.641, p = 0.002]. The model was validated in the second cohort (AUC = 0.621, p < 0.001). Finally, we merged both datasets to improve the precision of the model including HFHL in the first audiogram (OR = 3.168, p = 0.001), migraine (OR = 0.482, p = 0.036) and age of onset >35 years old (OR = 2.422, p = 0.006) as clinical predictors (AUC = 0.639, p < 0.001). CONCLUSIONS: A predictive model including the age of onset, HFHL in the first audiogram and migraine can help to assess the risk of bilateral SNHL in MD. This model may have significant implications for clinical management of patients with MD.

In-office endoscopic nasal polypectomy: prospective analysis of patient tolerability and efficacy.

PURPOSE: In-office rhinologic procedures have become popularised in the last decade, especially in North America. Endoscopic nasal polypectomy under local anaesthesia offers instant relief in selected patients with obstructive chronic rhinosinusitis with nasal polyps. We aimed to analyse patient tolerability during the procedure while measuring its effectiveness. METHODS: A prospective study of patients who underwent in-office microdebrider-assisted polypectomy under local anaesthetic from September 2018 to November 2019 in a Spanish tertiary hospital was performed. The tolerability was measured by monitoring vital signs during the procedure and using a visual analogue scale posteriorly. The effectiveness was calculated through patient-reported outcomes (SNOT-22) and endoscopic evaluation 1 and 6 months follow-up. RESULTS: Forty-four patients were included, with a mean age of 60.7 years. The mean visual analogue scale score was 2.76 out of 10 points. Vital signs were steady overall, with a statistically significant reduction (p < 0.001) in systolic pressure during the procedure. Presyncope and epistaxis were among the few mild complications. However, we registered one major complication that required intensive care admission. There was a 64% reduction in the SNOT-22 score in the first month, with a maintained effect after 6 months. Patients with asthma and a higher polyp load were the subgroups that required more time to achieve significant improvement. CONCLUSIONS: In-office polypectomy is a very effective technique that alleviates obstructive symptoms in patients with nasal polyposis, and it is generally safe and well tolerated when performed by an expert. However, rhinologists must be aware of potentially severe complications.

Coronary Heart Disease, Peripheral Arterial Disease, and Stroke in Familial Hypercholesterolaemia: Insights From the SAFEHEART Registry (Spanish Familial Hypercholesterolaemia Cohort Study).

OBJECTIVE: Heterozygous familial hypercholesterolemia (FH) is the most common premature atherosclerotic cardiovascular disease (ASCVD)-related monogenic disorder, and it is associated with ischemic heart disease. There is limited information whether FH increases the risk of peripheral arterial and cerebrovascular disease. Our aim was to analyze ASCVD prevalence and characteristics in different arterial territories in a large FH population, to compare them with an unaffected control population and to determine which factors are associated to ASCVD. APPROACH AND RESULTS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is an ongoing registry of molecularly defined patients with heterozygous FH in Spain. ASCVD in the different arterial territories was analyzed, as well as individual characteristics, genetic variables, and lipid-lowering therapies. The study recruited 4132 subjects (3745 ≥18 years); 2,752 of those enrolled were molecularly diagnosed FH cases. Median age was 44.0 years (45.9% men) and 40 years (46.6% men) in FH patients and unaffected relatives (P<0.001). ASCVD was present in 358 (13.0%) and 47 (4.7%) FH patients and unaffected relatives, respectively (P<0.001). History of premature ASCVD was more prevalent in FH patients (9.4% and 2.4% in FH patients and unaffected relatives, respectively; P<0.001). Coronary artery-related manifestations and peripheral artery disease were more prevalent in FH patients than in controls, but no significant differences were found for cerebrovascular events. Age, body mass index, type 2 diabetes mellitus, high blood pressure, previous use of tobacco, and lipoprotein(a) >50 mg/dL were independently associated with ASCVD. CONCLUSIONS: The prevalence of ASCVD is higher, and the involvement of the arterial territories is different in FH patients when compared with their unaffected relatives. Age, male sex, increased body mass index, hypertension, type 2 diabetes mellitus, smoking habit, and lipoprotein(a) >50 mg/dL were independently associated to ASCVD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02693548.

Antiadenohypophysis autoantibodies in patients with nongluten-related gastroenteropathies.

AIM: To investigate the presence of antipituitary antibodies (APA) in the serum of patients undergoing gastroenteropathies (GEP) other than celiac disease (CD). METHODS: APA were analyzed in GEP patients (n = 103), CD patients (n = 94), idiopathic growth hormone (GH) deficiency patients (n = 21), and 98 age- and sex-matched controls. Indirect immunofluorescence was performed in cryostat sections of baboon pituitary gland. RESULTS: APA were detected in 30% of GEP patients, 38% of them showed failure to thrive. No significant differences were found when we compared thrive impairment in negative and positive APA GEP patients. Indeed, normal values of insulin-like growth factor 1 were found in 93% of positive APA GEP patients. APA were detected in 52% of the CD patients. Ninety-one percent of them, in contrast to GEP group, showed significant growth impairment (P < 0.05) when compared to APA negative CD individuals. GH-deficient non-CD patients did not show APA. CONCLUSIONS: We have shown the presence of APA in patients with nongluten-related enteropathies. The presence of antipituitary autoantibodies in GEP patients does not seem to be associated with failure to thrive as it occurs in CD.

[Familial combined hyperlipidemia: consensus document]. / Hiperlipidemia familiar combinada: documento de consenso.

Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners.

Sudden Hearing Loss as an Initial Symptom of Vestibular Schwannoma.

OBJECTIVE: This study aims to determine the prevalence of vestibular schwannoma (VS) among patients presenting with sudden hearing loss (SHL) and to characterize the clinical features of individuals diagnosed with both VS and SHL. METHODS: We conducted an observational retrospective review at a tertiary referral center, spanning a 30-year period, focusing on patients diagnosed with SHL where VS was confirmed as the underlying cause. We included patients meeting these criteria while excluding those lacking imaging or with a pre-existing diagnosis of VS. We evaluated the audiological characteristics at the time of diagnosis and assessed clinical outcomes following treatment. RESULTS: Among the 403 patients presenting with SHL during the study period, 9 (2.2%) were diagnosed with VS, aged between 25 and 72 years. Although audiometric profiles varied, high-frequency hearing loss predominated, mostly categorized as mild to moderate. Six patients (66%) had Koos grade I-II schwannomas. Only 2 patients achieved complete hearing recovery post-treatment, while 4 showed no improvement. CONCLUSIONS: VS is a rare etiology of SHL, accounting for slightly over 2% of cases. Its symptomatology, severity, and audiometric patterns do not significantly differ from SHL caused by other factors. Tumor size does not correlate with hearing characteristics. Treatment modalities resemble those for other SHL cases, and hearing improvement does not obviate the necessity for follow-up magnetic resonance imaging (MRI) scans.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

A novel phenotype variant of severe congenital neutropenia caused by G6PC3 deficiency.

Severe congenital neutropenia type 4 (SCN4) is associated with mutations in the G6PC3 gene. To date, all patients bearing the p.Gly260Arg variant of the G6PC3 gene show heart defects. Here, we present a case of the p.Gly260Arg variant in a patient who did not have structural or functional heart anomalies. Treatment with granulocyte colony-stimulating factor recovered the absolute neutrophil count and neutrophil functional competence.

Persistence with long-term PCSK9 inhibitor treatment and its effectiveness in familial hypercholesterolaemia: data from the SAFEHEART study.

AIMS: Most heterozygous familial hypercholesterolaemia (FH) patients require intensive lipid-lowering therapy (LLT) including PCSK9 inhibitors (PCSK9is) to reach current low-density lipoprotein cholesterol (LDL-C) goals. Persistence with chronic treatment is important to reduce the burden of atherosclerotic cardiovascular disease. We analysed persistence, efficacy, and impact on quality of life (QoL) of PCSK9i in FH patients in clinical practice setting. METHODS AND RESULTS: Spanish Familial Hypercholesterolaemia Cohort Study (SAFEHEART) is an open, prospective study in genetically defined FH patients in Spain. Patients ≥18 years of age (n = 696, 46% females) on stable LLT treated with PCSK9i were analysed. Median LDL-C at starting PCSK9i was 145 mg/dL [interquartile range (IQR), 123-177], 3.8 mmol/L (IQR 3.2-4.6). After a median follow up of 3.7 years (IQR 2.3-4.8), 27 patients (4%) discontinued PCSK9i treatment: 5 temporarily (0.7%) and 22 permanently (3.2%). Persistence with PCSK9i was 96.1% in the whole period. Median LDL-C levels and % LDL-C reduction attained after 1 year of treatment and in the last follow-up visit were 63 mg/dL (IQR 43-88), 1.6 mmol/L (IQR 1.1-2.23); 61 mg/dL (IQR 44-82), 1.6 mmol/L (IQR 1.1-2.1); 57.6% (IQR 39.5-69); and 58% (IQR 44-68), respectively. 2016 and 2019 ESC/EAS LDL-C goals were attained by 77 and 48% of patients, respectively, at the last follow-up visit (P < 0.001). Mean QoL score increased slightly in the first year and remained stable. CONCLUSION: Long-term persistence with PCSK9i in FH patients is very high, with a good QoL. Effectiveness in LDL-C reduction and LDL-C goal achievement dramatically improved with PCSK9i in this high-risk population in clinical practice setting. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02693548.

The endocytic adaptor Numb regulates thymus size by modulating pre-TCR signaling during asymmetric division.

Stem cells must proliferate and differentiate to generate the lineages that shape mature organs; understanding these 2 processes and their interaction is one of the central themes in current biomedicine. An intriguing aspect is asymmetric division, by which 2 daughter cells with different fates are generated. Several cell fate determinants participate in asymmetric division, with the endocytic adaptor Numb as the best-known example. Here, we have explored the role of asymmetric division in thymocyte development, visualizing the differential segregation of Numb and pre-TCR in thymic precursors. Analysis of mice where Numb had been inhibited by expressing a dominant negative revealed enhanced pre-T-cell receptor (TCR) signaling and a smaller thymus. Conversely, Numb overexpression resulted in loss of asymmetric division and a larger thymus. The conclusion is that Numb determines the levels of pre-TCR signaling in dividing thymocytes and, ultimately, the size of the pool from which mature T lymphocytes are selected.

Clinical Impact of Genetic Diagnosis of Sensorineural Hearing Loss in Adults.

HYPOTHESIS: Adult genetic sensorineural hearing loss (SNHL) may be underestimated. BACKGROUND: The diagnosis of genetic hearing loss is challenging, given its extreme genetic and phenotypic heterogeneity, particularly in adulthood. This study evaluated the utility of next-generation sequencing (NGS) in the etiological diagnosis of adult-onset SNHL. MATERIALS AND METHODS: Adults (>16 yr old) with SNHL were recruited at the Otolaryngology Department at Marqués de Valdecilla University Hospital (Spain). Environmental factors, acoustic trauma, endolymphatic hydrops, and age-related hearing loss were excluding criteria. An NGS gene panel was used, including 196 genes (OTOgenics v3) or 229 genes (OTOgenics v4) related to syndromic and nonsyndromic hearing loss. RESULTS: Sixty-five patients were included in the study (average age at the onset of SNHL, 41 yr). Fifteen pathogenic/likely pathogenic variants considered to be causative were found in 15 patients (23% diagnostic yield) in TECTA (4), KCNQ4 (3), GJB2 (2), ACTG1 (1), COL2A1 (1), COCH (1), COCH/COL2A1 (1), STRC (1), and ABHD12 (1). Three patients had syndromic associations (20% of patients with genetic diagnosis) that had not been previously diagnosed (two Stickler type I and one polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract syndrome). Seven variants of unknown significance were found in COL11A1 (1), GSMDE (2), DNTM1 (1), SOX10 (1), EYA4 (1), and TECTA (1). CONCLUSION: NGS gene panels can provide diagnostic yields greater than 20% for adult SNHL, with a significant proportion of variant of unknown significance that could potentially contribute to increasing diagnostic output. Identifying a genetic cause enables genetic counseling, provides prognostic information and can reveal unrecognized syndromes contributing to an accurate management of their associated manifestations.

Checklist of the temporal bone and lateral skull base CT-scan.

Computed tomography scan of the temporal bone is a fundamental imaging modality for both the diagnosis and treatment of a wide range of pathologies affecting this complex structure. Temporal bone computed tomography scan provides a more detailed depiction of bone structures, compared with magnetic resonance imaging and, for this reason computed tomography scan is the imaging modality of choice in the planning of otological surgery. The aim of this article is to present a checklist to allow the otolaryngologist to assess systematically and in an organized manner the main anatomical landmarks, anatomical variants, as well as the most common postoperative surgical changes, which can be identified before any safe otological surgery. This revision was promoted by the Spanish Society of Otolaryngology and elaborated in a checklist template divided into the different areas of the temporal bone and the lateral skull base.

Hormone replacement therapy in children with growth hormone deficiency: impact on immune profile.

Growth hormone (GH) may influence the immune system. The aim of this study was to assess the immune profile after treatment with GH in pre-pubertal children with a deficiency of this hormone. The study was carried out in two phases. Two groups were included in the first phase: group A) children treated with GH; group B) untreated children, prior to starting treatment. In the second phase, group B children were assessed 6 months after starting treatment. In the first phase, groups A and B were compared (case-control study). In the second phase, group B was compared in terms of baseline and final times (before and after study). We analysed: humoral immunity (immunoglobulin (Ig)A, IgG, IgM, C1 inhibitor, C3, and C4) and cell-mediated immunity (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+ lymphocytes, and natural killer (NK) cells). Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) were also determined. In the first phase, CD3+, CD4+, CD19+, and NK cells and CD4+/CD8+ were greater in the treated group. CD8+ was lower in this group. No variations were seen in immunoglobulins and the complement between both groups. There were no changes to the complement in either of the two phases. In the second phase, untreated patients were assessed after 6 months of treatment. When comparing the baseline and final immune profiles, a statistically significant decrease in IgG and IgM was observed, and an increase of IGF-1 levels and monocytes. In conclusion, our study shows changes in the cellular and humoral immune profiles in children with GH deficiency who were treated.

Efficacy of PCSK9 inhibitors in the treatment of heterozygous familial hypercholesterolemia: A clinical practice experience.

BACKGROUND: PCSK9 inhibitors are a treatment option for patients with familial hypercholesterolemia not on low-density lipoprotein cholesterol goals despite the use of maximally tolerated high intensity-statins dose. OBJECTIVE: To evaluate the efficacy of alirocumab and evolocumab in LDL-C reduction and targets attainment in patients with heterozygous familial hypercholesterolemia in clinical practice setting. METHODS: SAFEHEART is an open, long-term prospective study of a cohort of subjects with molecular diagnosis of familial hypercholesterolemia. This study analyze subjects ≥ 20 years of age on stable lipid-lowering therapy, who received PCSK9 inhibitors during the period 2016 to January 2020. RESULTS: 433 patients (mean age 55 years, 53% male, 39% with cardiovascular disease) were included and followed-up for a median of 2.5 years (IQR 1.6-3.0). Median LDL-C level prior to PCSK9 inhibitors was 145 mg/dL (IQR 125-173). The addition of PCSK9 inhibitors (211 alirocumab, 222 evolocumab) reduced LDL-C by 58% (IQR 41-70) p<0.001, in men and women, achieving a median LDL-C level of 62 mg/dL (IQR 44-87) without differences between both PCSK9 inhibitors. Out of them 67% with and 80% without cardiovascular disease reached 2016 ESC/EAS LDL-C targets, and 46% very high risk and 50% high risk patients achieved 2019 ESC/EAS LDL-C goals. Independent predictor factors for attainment of 2019 ESC/EAS LDL-C goals were to be male, smoking and the use of statins with ezetimibe. Both inhibitors were well tolerated. CONCLUSIONS: PCSK9 inhibitors on top of maximum lipid-lowering treatment significantly reduced LDL-C levels in patients with familial hypercholesterolemia and improved the achievement of LDL-C targets.

Exploring the frontiers of vestibular migraine: A case series.

INTRODUCTION: Patients with episodic vestibular syndrome (EVS) whose symptoms resemble those of vestibular migraine (VM) but who do not meet the criteria for it are common. OBJECTIVE: To describe those patients suffering from EVS in whom defined etiologies have been ruled out in order to determine if their symptoms can be linked to VM. MATERIAL AND METHODS: Prospective multicenter study. The medical records of patients with VM and patients with EVS suggestive of VM but not meeting the criteria for it were examined. The characteristics of headache, the number and the length of attacks, the association of vestibular symptoms and headache, the intensity of symptoms and the response to treatment were recorded. RESULTS: 58 patients met the criteria for VM or probable VM; 30 did not. All of the symptoms improved significantly in the treated patients with VM or probable VM; in the rest of the treated patients, only the vestibular symptoms improved. CONCLUSION: A subgroup of patients that cannot be attributed to any known vestibulopathy according to present day VM criteria profited from migraine treatment, suggesting that their vestibular symptoms belong to the migraine spectrum; whereas some do not, yet our analysis could not identify distinctive features that allowed subgroup attribution.

Lack of cytomegalovirus (CMV)-specific cell-mediated immune response using QuantiFERON-CMV assay in CMV-seropositive healthy volunteers: fact not artifact.

The QuantiFERON-CMV (QF) assay measures cell-mediated immunity against cytomegalovirus (CMV-CMI), which is particularly useful in individuals susceptible to CMV infection such as transplant patients. A positive QF result identifies patients that are better protected against CMV infection. However, the significance of a negative QF result in CMV-seropositive individuals needs to be clarified. CMV-CMI was analyzed in healthy subjects using the QF assay, and, in parallel, the Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA). FASCIA assay measures T-cell proliferation using CMV lysate as stimulus whereas QF assay use a mix of peptides. A total of 93 healthy volunteers were enrolled, and 13/71 CMV-seropositive individuals (18.3%) showed humoral/cellular discordance using QF assay (CMV+ QF-). Interestingly, with FASCIA assay CD4+ and CD8+ T-cell proliferations were lower in CMV+ QF- than in CMV+ QF+ individuals. Furthermore, CMV+ QF- volunteers had a lower level of anti-CMV IgG than CMV+ QF+ subjects. Discordant CMV+ QF- volunteers can be defined as low responder individuals since they show lower CMV-specific humoral and cellular immune responses in comparison to CMV+ QF+ individuals. Immune discordance shows the high heterogeneity of immunity to CMV in healthy subjects.

Subjective benign paroxysmal positional vertigo in patients with osteoporosis or migraine.

INTRODUCTION: Subjective benign paroxysmal positional vertigo is a form of benign paroxysmal positional vertigo in which during the diagnostic positional maneuvers patients only present vertigo symptoms with no nystagmus. OBJECTIVE: To study the characteristics of subjects with subjective benign paroxysmal positional vertigo. METHODS: Prospective multicenter case-control study. All patients presenting with vertigo in the Dix-Hallpike test that presented to the participating hospitals were included. The patients were separated into two groups depending on whether nystagmus was present or not. An Epley Maneuver of the affected side was performed. In the follow-up visit, patients were checked to see if nystagmus and vertigo were present. Both groups of patients were compared to assess the success rate of the Epley maneuver and also to compare the presence of 19 variables. RESULTS: 259 patients were recruited, of which 64 belonged to the subjective group. Nystagmus was eliminated in 67.2% of the patients with benign paroxysmal positional vertigo. 89.1% of the patients with subjective benign paroxysmal positional vertigo remained unaffected by nystagmus, thus showing a significant difference (p=0.001). Osteoporosis and migraine were the variables which reached the closest to the significance level. In those patients who were taking vestibular suppressors, the percentage of subjective benign paroxysmal positional vertigo was not significantly higher. CONCLUSIONS: Subjective benign paroxysmal positional vertigo should be treated using the Epley maneuver. More studies are needed to establish a relationship between osteoporosis, migraine and subjective benign paroxysmal positional vertigo. The use of vestibular suppressants does not affect the detection of nystagmus.