Thrombin generation in patients with idiopathic sudden sensorineural hearing loss

Introduction

The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unknown. Systemic hemostasis derangement causing local vascular occlusion might be one of the pathogenetic mechanisms.

Material and Methods

Forty-one patients with ISSNHL and 48 healthy subjects were investigated. We measured thrombin generation in the presence or absence of thrombomodulin in platelet-poor or platelet-rich plasma by means of a home-made method based on calibrated automated thrombin generation, which should mimic much more closely than any other conventional coagulation test the balance of coagulation operating in vivo. DNA analyses for the most common prothrombotic genotypes such as factor V Leiden, prothrombin G20210A, MTHFR or platelet GPIIIa A1/A2 were also carried out in patients and controls.

Results

Patients generated as much thrombin as controls both in platelet-rich and platelet-poor plasma and the frequency of the most common prothrombotic genotypes were similar in patients and controls.

Conclusions

The results suggest that the pathogenesis of ISSNHL is not due to systemic blood hypercoagulability. Other culprits such as local vascular abnormalities, viral infections, immune-mediated mechanisms or abnormalities of inner ear and central nervous system should be advocated to explain ISSNHL.     

Cortical reorganization in children with unilateral sensorineural hearing loss

Previous studies have shown evidence of cortical reorganization following unilateral sensorineural hearing loss (USNHL). In addition, study participants with right USNHL have shown greater deficits in academic and language performance compared with those with left USNHL. A preliminary functional magnetic resonance imaging investigation was performed on a small cohort of participants, four with left USNHL and four with right USNHL, using the paradigm of listening to random tones. While the participants with left USNHL displayed greater activation in the right superior temporal gyrus, those with right USNHL displayed greater activation in the left inferior frontal area immediately anterior to the superior temporal gyrus. The results provide preliminary evidence of disparate neural circuitry supporting auditory processing in participants with left and right USNHL.     

特发性突聋远期预后的临床观察

目的探讨特发性突聋远期预后与近期预后之间的差异,评价当前综合治疗对远期预后的影响。方法 24例患者分别于入院、出院及出院后〉6个月分别进行纯音听阈检测。以出院时听力状态为近期预后指标,出院后〉6个月时听力状态为远期预后指标。远期预后与近期预后的比较采用非参数秩和检验。结果近期有效率为45.8%,远期好转率为62.5%,差异有统计学意义（P〈0.05）。结论特发性突聋远期预后与近期预后不同,远期预后优于近期预后,患者的听力恢复是一个漫长的过程。     

Bilateral sequential sudden sensorineural hearing loss in protein S deficiency

Journal of Neurology -     

以突聋为首发症状的脑梗死患者临床特点

目的探讨以突聋为首发症状的脑梗死患者的临床特点,提高对该类情况的认识,尽早做出正确诊断。方法报道我院2014年收治的2例以突聋为首发症状的脑梗死病例,均完善头颅MRI、HR-MRI、DSA、颈动脉超声、TCD检查,结合文献复习,总结临床特点。结果该2例患者首发症状表现为突聋合并头晕,DSA均发现基底动脉近段狭窄。病例1头颅MRI示双侧桥脑及左侧小脑新发梗死灶,予急诊动脉溶栓治疗,后续双联抗血小板聚集及他汀治疗,听力好转。病例2头颅MRI示右侧桥脑新发梗死灶,予双联抗血小板聚集及他汀治疗,遗留听力下降。结论以突聋为首发症状的脑梗死并不罕见,突聋患者应尽快完善脑血管检查,突聋患者具有以下临床特点时需要高度警惕脑梗死:伴随头晕症状、合并多种动脉粥样硬化危险因素、基底动脉狭窄。     

Progressive sensorineural hearing loss in childhood

A progressive sensorineural hearing loss in childhood, with an extremely variable prevalence (from 4% to 30%), has been reported in the literature. This wide range of reported figures could depend on the different criteria used for identifying the deterioration, the groups, and the examined age ranges. The most frequent etiology of progressive sensorineural hearing loss in childhood includes hereditary causes, both syndromic and nonsyndromic, and developmental and infectious causes, whereas metabolic, toxic, autoimmune, traumatic, and vascular etiologies are less common; however, the origin of the hearing impairment often remains unknown. The population for this study consisted of 178 children with bilateral sensorineural hearing loss who were examined between 1971 and 1993 using audiologic tests. Syndromal genetic hearing loss was excluded from the study. A progressive loss of acuity was found in 11 subjects, with a prevalence of 6.2%. The etiology was hereditary deafness in five patients, congenital infection in one, and congenital inner ear anomaly in another patient; in the last four children the etiology was unknown. Onset of deterioration was after 4 years of age in 73% of the patients. The progressive evolution was binaural in almost all patients (10 of 11) and asymmetric in most, with a tendency to a greater deterioration at the frequencies initially least affected.     

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.     

Unusual findings in brain biopsies of two patients with acute magnetic resonance imaging lesions associated with focal seizures

PURPOSE: Patients with focal seizures often have magnetic resonance imaging (MRI) abnormalities in the brain region of their presumed seizure focus. Neoplasms, ischemic infarctions, inflammatory processes, and other specific pathologic entities have been diagnosed by biopsies of such MRI abnormalities. Two patients with this presentation had brain lesion biopsies with a leading presumptive diagnosis of glial neoplasm but were found to have indistinct histopathology. METHODS: Each patient was initially seen with focal seizures (right parietal region, right hippocampus) corresponding with focally increased T2 signal on MRI. In both patients, the preoperative clinical suspicion was for neoplastic or inflammatory processes. RESULTS: Several weeks after seizure onset, craniotomy in patient 1 and stereotactic needle biopsy in patient 2 revealed mild gliosis with reactive vascular changes and perivascular hemosiderin deposition, not diagnostic of but compatible with venous congestion (or possibly venous thrombosis). Postoperatively, patient 1 had brief sensory seizures that stopped 5 months after surgery, whereas subsequent seizures did not develop in patient 2. Both patients had normalization of their MRI (except for postoperative changes) and have remained seizure free. CONCLUSIONS: We describe two patients who had brain biopsies of striking focal increased T2 signal MRI abnormalities associated with seizures. Pathologic findings contradicted our preoperative suspicions (neoplasm or inflammatory process), compatible with (but not conclusive for) subacute venous congestion/thrombosis. These findings indicate that patients with seizures may have an associated discrete intraaxial MRI lesion that is not neoplastic. To our knowledge, this is the first report of focal seizure-associated MRI lesions with biopsy findings compatible with venous congestion/thrombosis.     

Leptomeningeal carcinomatosis: an unusual cause of sudden onset bilateral sensorineural hearing loss.

We report a 66-year-old woman who developed sudden-onset bilateral sensorineural deafness due to leptomeningeal carcinomatosis involving the vestibulocochlear nerves. The clinical and diagnostic features of leptomeningeal carcinomatosis are discussed.     

Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings

neurogenetics - TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible...     

Intravascular lymphomatosis presenting with sudden hearing loss

Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation of malignant large cell lymphoma cells in small vessels. Neurological manifestations are typically the initial and, often the only, clinically obvious consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem demonstration of the intravascular tumor. We report a patient in whom sudden hearing loss heralded IVL and propose that the hearing loss may have been the consequence of labyrinthine infarction consequent to the aggregation of malignant cells in the internal auditory artery.     

Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study

Aim The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness. Method One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5y 7mo, SD 3y 6mo, range 8mo–16y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment. Results Forty‐eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural–emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty‐seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001). Interpretation A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.     

Cytomegalovirus-induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice

Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL) in children. During murine (M)CMV-induced encephalitis, the immune response is important for both the control of viral dissemination and the clearance of virus from the brain. While the importance of CMV-induced SNHL has been described, the mechanisms surrounding its pathogenesis and the role of inflammatory responses remain unclear. This study presents a neonatal mouse model of profound SNHL in which MCMV preferentially infected both cochlear perilymphatic epithelial cells and spiral ganglion neurons. Interestingly, MCMV infection induced cochlear hair cell death by 21 days post-infection, despite a clear lack of direct infection of hair cells and the complete clearance of the virus from the cochlea by 14 dpi. Flow cytometric, immunohistochemical, and quantitative PCR analysis of MCMV-infected cochlea revealed a robust and chronic inflammatory response, including a prolonged increase in reactive oxygen species production by infiltrating macrophages. These data support a pivotal role for inflammation during MCMV-induced SNHL.     

Vascular risk factors in sudden hearing loss

Low density lipoprotein (LDL) and fibrinogen apheresis was recently reported to be an effective therapy in sudden hearing loss (SHL). In this study, we investigated whether lipoprotein and/or fibrinogen plasma concentrations, related gene polymorphisms and other cardiovascular risk factors are also risk factors for SHL. Total cholesterol, HDL and LDL cholesterol plasma concentrations, fibrinogen levels, and two functionally relevant fibrinogen polymorphisms were determined in 142 consecutive patients and in 84 age- and sex-matched control subjects of the same ethnic background, using routine laboratory methods and PCR analysis. In addition, we determined the platelet glycoprotein Ia (GPIa) C807T polymorphism, which was recently proposed to be a genetic risk factor for SHL, and we compared the patients' and controls' clinical characteristics. Total and LDL cholesterol concentrations were not different between patients and controls. Fibrinogen plasma levels were significantly increased in SHL patients (260+/-57 vs. 239+/-110 mg/dl, p=0.002). However, fibrinogen was not related to SHL in multivariate analysis, and none of the investigated fibrinogen polymorphisms was associated with SHL. By contrast, T allele carriers of the GPIa 807 polymorphic site had an increased risk to develop SHL (OR 1.81) and were more likely not to recover from SHL, compared to C allele carriers (OR 3.0). Moreover, significantly more SHL patients were current smokers (56.3% vs. 19.3% in the control group, p<0.0001). In conclusion, there is a partial overlap between classical coronary risk factors and risk factors for SHL. Hypercholesterolemia and hypoalphalipoproteinemia (low HDL cholesterol levels) are apparently no major risk factors for SHL, whereas the GPIa C807T polymorphism, elevated fibrinogen levels, and smoking are associated with an increased risk for SHL. Altogether these findings suggest a vascular involvement in the pathogenesis of SHL and may have important implications for the development of therapeutic and preventive strategies.     

Cranial magnetic resonance imaging findings in children with nonsyndromic mitochondrial diseases

Cranial magnetic resonance imaging findings suggestive of specific mitochondrial syndromes are reported. However, cranial magnetic resonance imaging features in children with nonsyndromic mitochondrial diseases are rarely described. From January 1992-September 2009, data from 33 patients with nonsyndromic mitochondrial diseases were collected. We investigated cranial magnetic resonance imaging features in children with nonsyndromic mitochondrial diseases, and identified potential diagnostic characteristics. Eleven of 33 patients (33.3%) demonstrated normal findings, and 22 (66.7%) demonstrated abnormal findings. The most common abnormal finding was cerebral atrophy, with or without other lesion sites (15/33; 45.5%). The second most common was bilateral basal ganglia involvement (6/33; 18.2%). Follow-up imaging was performed in 20 patients. Ten of these 20 (50.0%) demonstrated evolutionary changes, in which progressive global brain atrophy was evident. Three patients with normal results and one patient with cerebral atrophy on initial imaging demonstrated prominent signal changes over the basal ganglia, brainstem, gray matter, white matter, and bilateral cerebellar hemispheres on follow-up imaging. Imaging in children with nonsyndromic mitochondrial diseases may produce variable findings. Normal results and cerebral atrophy on the initial cranial magnetic resonance imaging are commonly evident in this patient group.     

Abnormal neuroanatomy in a nonretarded person with autism. Unusual findings with magnetic resonance imaging

Recent studies of infantile autism using computed tomographic scanning emphasized the importance of studying cases of classic autism (Kanner's syndrome) without complicating conditions such as mental retardation. Computed tomographic scan studies of such patients reported no evidence of anatomical abnormalities of cerebral hemispheres or of subcortical structures, which are defined by landmarks such as the lateral ventricles and lentiform nuclei. Examination of the cerebellum was not mentioned. The most recent postmortem neuropathologic study reported significant cerebellar abnormality, but the study was of a severely retarded autistic individual. Using magnetic resonance imaging, we have found in vivo evidence of a significant and unusual cerebellar malformation in a person with the classic form of autism uncomplicated by mental retardation (current nonverbal IQ = 112), epilepsy, history of drug use, postnatal trauma, or disease. The finding showed hypoplasia of the declive, folium, and tuber in posterior vermis, but not of the anterior vermis, and hypoplasia of only the medial aspect of each cerebellar hemisphere. The right posterior cerebral hemisphere also showed pathologic findings.