Sjögren's syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a wide spectrum of sensory modalities and distribution patterns. The objective of this ...cross-sectional study was to determine characteristics of Sjögren's syndrome as a cause for severe neuropathy with limb weakness.
One hundred and eighty four patients with polyneuropathy associated with limb weakness underwent routine diagnostics including investigations for Sjögren's syndrome. Forty-four patients with Sjögren's syndrome (ACR-EULAR classification criteria) and severe neuropathy were identified.
Sjögren's syndrome was found at a median age of 63 years and the gender distribution showed a balanced female-male ratio of 1:1. Anti-SSA(Ro) antibodies were detected in 48% while seronegative patients were diagnosed with Sjögren's syndrome based on sialadenitis on minor salivary gland biopsy with a focus score ≥1. The majority of patients (93%) were diagnosed with Sjögren's syndrome after neurological symptoms appeared. Limbs were symmetrically involved in 84% of patients (57% tetraparesis, 27% paraparesis). Sensory function was not affected in 11% of patients indicating that Sjögren's syndrome associated neuropathy can present as a pure motor syndrome. Electrophysiological measurements did not reveal pathognomonic findings (23% demyelinating pattern, 36% axonal pattern, 41% both demyelinating and axonal damage signs). More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging.
Our findings show that severe neuropathy with limb weakness is often associated with Sjögren's syndrome. This is of great importance in identifying and understanding the causes of immune mediated polyneuropathy.
In a previous study, an inner ear catheter was used to deliver low- and high-dose steroids into the cochlea prior to cochlear implant electrode insertion. With this approach, more apical regions of ...the cochlea could be reached and a reduction of electrode impedances in the short term was achieved in cochlear implant recipients. Whether intracochlear application of drugs via the catheter is a safe method also for patients with residual hearing has not been investigated hitherto. The aim of the present study was therefore to investigate the effect of intracochlear triamcinolone application in cochlear implant recipients with residual hearing.
Patients with residual hearing were administered triamcinolone-acetonide (4 mg/ml;
= 10) via an inner ear catheter just prior to insertion of a MED-EL FLEX28 electrode. Impedances were measured at defined time points (intra-operatively, post-operatively and at first fitting) and retrospectively compared with a control group (no steroid application) and low- and high-dose group. Hearing thresholds were measured preoperatively, 3 days after surgery and at first fitting by pure tone audiometry. Pre- to postoperative hearing loss was determined at first fitting and compared to results from a previous study.
The median hearing loss after implantation (125-1,500 Hz) was 20.6 dB. Four patients (40%) showed a median hearing loss of less than 15 dB, three patients (30%) between 15 and 30 dB and three patients (30%) more than 30 dB. The median hearing loss was similar to the results obtained from our previous study showing a median hearing loss of 24 dB when using FLEX28 electrode arrays.
No difference in residual hearing loss was found when comparing application of triamcinolone-acetonide using an inner ear catheter prior to the insertion of a FLEX28 electrode array to the use of the FLEX28 electrode array without the catheter. Thus, we conclude that application of drugs to the cochlea with an inner ear catheter could be a feasible approach in patients with residual hearing.
Administration of low-dose steroids via a catheter inserted into the cochlea to apply pharmaceuticals to more apical regions was previously shown not to be sufficient for long-term reduction of ...electrode impedances. The aim of the present study was to investigate the effect of intra-cochlear high-dose triamcinolone application on impedances in cochlear implant recipients. Patients received low-dose (4 mg/ml;
= 5) or high-dose (20 mg/ml;
= 5) triamcinolone via a cochlear catheter just prior to the insertion of a Med-El Flex28 electrode. Impedances were measured at defined time points from intra-operatively up to 12 months after first fitting and retrospectively compared with a control group (no steroid application). Patients who received a high-dose application of crystalloid triamcinolone showed significantly reduced impedances in the first fitting measurements compared to the control group. This effect was no longer detectable in patients of the low-dose group at that time. Looking at the different regions of the electrode, the impedance values were lowered significantly only at the basal and medial contacts. At later time points, there were no significant differences between any of the groups. This is the first study to demonstrate a dose-dependent reduction of impedances by deep intra-cochlear injection of triamcinolone in cochlear implant patients. With a high-dose, single application of triamcinolone using a cochlear catheter prior to insertion of a Flex28 electrode, the impedances can be significantly reduced up to and including the first fitting. Although the effect was longer lasting than when compared to low-dose triamcinolone, it was also not permanent.
Suppression of foreign body reaction, improvement of electrode-nerve interaction, and preservation of residual hearing are essential research topics in cochlear implantation. Intracochlear pharmaco- ...or cell-based therapies can open new horizons in this field. Local drug delivery strategies are desirable as higher local concentrations of agents can be realized and side effects can be minimized compared to systemic administrations. When administered locally at accessible, basal parts of the cochlea, drugs reach apical regions later and in much lower concentrations due to poor diffusion patterns in cochlear fluids. Therefore, new devices are needed to warrant rapid distribution of agents into all parts of the cochlea. Five patients received a deep intracochlear injection of triamcinolone with a specifically designed cochlear catheter during cochlear implantation right before inserting a cochlear implant electrode. As a measure for formation of fibrous tissue around the electrode, electrical impedances were measured in the operation room and over 4 months thereafter. No adverse events were observed peri- and postoperatively. The handling of the device was easy. Severe damage to the microstructure of the cochlea was excluded as far as possible by cone beam computed tomography and vestibular testing. A delayed rise of the impedances was seen in the catheter group compared to controls over all regions of the cochlea. A statistical significance, however, was only obtained at the midregion of the cochlea. Consequently, the cochlear catheter is a safe and feasible device for local drug delivery of pharmaceutical agents into deeper regions of the cochlea.
The molecular pathomechanisms in the majority of patients suffering from acute or progressive sensorineural hearing loss cannot be determined yet. The size and the complex architecture of the cochlea ...make biopsy and in-depth histological analyses impossible without severe damage of the organ. Thus, histopathology correlated to inner disease is only possible after death. The establishment of a technique for perilymph sampling during cochlear implantation may enable a liquid biopsy and characterization of the cochlear microenvironment. Inflammatory processes may not only participate in disease onset and progression in the inner ear, but may also control performance of the implant. However, little is known about cytokines and chemokines in the human inner ear as predictive markers for cochlear implant performance. First attempts to use multiplex protein arrays for inflammatory markers were successful for the identification of cytokines, chemokines, and endothelial markers present in the human perilymph. Moreover, unsupervised cluster and principal component analyses were used to group patients by lead cytokines and to correlate certain proteins to clinical data. Endothelial and epithelial factors were detected at higher concentrations than typical pro-inflammatory cytokines such as TNF-a or IL-6. Significant differences in VEGF family members have been observed comparing patients with deafness to patients with residual hearing with significantly reduced VEGF-D levels in patients with deafness. In addition, there is a trend toward higher IGFBP-1 levels in these patients. Hence, endothelial and epithelial factors in combination with cytokines may present robust biomarker candidates and will be investigated in future studies in more detail. Thus, multiplex protein arrays are feasible in very small perilymph samples allowing a qualitative and quantitative analysis of inflammatory markers. More results are required to advance this method for elucidating the development and course of specific inner ear diseases or for perioperative characterization of cochlear implant patients.
To evaluate a possible correlation between impedance values and speech perception after cochlear implantation.
Retrospective chart review.
Tertiary referral center.
All patients implanted with a ...MedEl Flex28 device in our department with complete audiometric data (Freiburger monosyllabic testing at 65 dB, Hochmaier-Schulz-Moser testing in quiet and in 10 dB noise) and impedance measurements at the 1-year refitting appointment were enrolled in this study. Further inclusion criteria were age > 17 years, native speakers, and no use of electric-acoustic-stimulation.
Mean values for impedances were calculated over all electrode contacts and separately for basal, medial, and apical regions. These data were correlated statistically (Pearson's correlation) with speech testing results. Furthermore, groups of patients with extreme values were built and compared against each other and against the rest of the collective.
Impedance values did not correlate significantly with speech performance in any of the audiometric tests neither for all electrode contacts nor for specific clusters of contacts. Patients with the lowest impedances did not perform statistically different than patients with the highest impedances in any condition.
To our knowledge, this is the first data on a possible correlation between impedances and speech perception. The extent of the impedances as a benchmark for a good performance in speech discrimination tests could not be verified. Further prospective studies, possibly with more precise diagnostic tools, should be carried out to define the value of impedance measurements for cochlear implantation provision.
Background and Purpose
The phenotype of Sjögren's syndrome‐associated neuropathy has been better characterized in recent years. However, Sjögren's syndrome‐associated neuropathy remains an ...underdiagnosed entity with only few insights considering the pathomechanisms of nerve damage. Nerve ultrasound has proven to be a useful and efficient tool in detecting nerve damage of autoimmune origin. We, therefore, aimed to evaluate this method for Sjögren's syndrome‐associated neuropathy.
Methods
Patients with Sjögren's syndrome and clinical signs of neuropathy underwent sonographic examination of both median and ulnar nerves. Nerve thickening was classified for cross‐sectional areas of >12 mm² at the median nerve and for >10 mm² at the ulnar nerve. Fascicle thickening was documented for cross‐sectional areas ≥5 mm² at the median and ≥3 mm² at the ulnar nerve.
Results
Forty‐three patients were included in the analysis (median age 60 years interquartile range 53–73 years, female rate 60%). 31/43 patients (72%) showed abnormalities on nerve ultrasound, while nerve thickening was found more frequently than fascicle thickening (90% vs. 52% of patients with sonographic abnormalities, respectively). Abnormal findings were observed more frequently at the median nerve and in proximal localization. Abnormal findings on nerve conduction studies were evident in 36/43 patients (84%). Nerve conduction studies revealed a tendency of demyelinating nerve damage patterns being associated with abnormal findings on nerve ultrasound.
Conclusions
In addition to nerve conduction studies, nerve ultrasound may have a supporting role in the diagnosis of Sjögren's syndrome‐associated neuropathy. Also, our data support an immune‐mediated inflammatory demyelinating pathogenesis of Sjögren's syndrome‐associated neuropathy.
The desired outcome of the implantation of active middle ear implants is maximum coupling efficiency and a minimum of conductive loss. It has not been investigated yet, which loading forces are ...applied during the process of coupling, which forces lead to an optimum actuator performance and which forces occur when manufacturer guidelines for coupling are followed.
Actuator output was measured by laser Doppler vibrometry of stapes motion while the actuator was advanced in 20 μm steps against the incus body while monitoring static contact force. The occurrence of conductive losses was investigated by measuring changes in stapes motion in response to acoustic stimulation for each step of actuator displacement. Additionally, the electrical impedance of the actuator was measured over the whole frequency range at each actuator position.
Highest coupling efficiency was achieved at forces above 10 mN. Below 1 mN no efficient coupling could be achieved. At 30 mN loading force, which is typical when coupling according to manufacturer guidelines, conductive losses of more than 5 dB were observed in one out of nine TBs. The electrical impedance of the actuator showed a prominent resonance peak which vanished after coupling.
A minimum coupling force of 10 mN is required for efficient coupling of the actuator to the incus. In most cases, coupling forces up to 100 mN will not result in clinically relevant conductive losses. The electrical impedance is a simple and reliable metric to indicate contact.
Objective
Extraglandular neurological manifestations of Sjögren’s syndrome are increasingly recognized, defining the disease entity of Neuro‐Sjögren. Neuropsychological assessment of patients with ...Sjögren’s syndrome has hitherto been performed on predominantly rheumatological cohorts. These studies revealed a wide variety of prevalence rates for cognitive impairment (22–80%), while variable cut‐off criteria for detection of cognitive impairment were applied. Attentional functions have not yet been thoroughly investigated in these patients, although they clearly represent relevant aspects of cognitive functioning in daily life.
Methods
We therefore conducted extensive neuropsychological assessment based on two neuropsychological test batteries i.e., the extended German version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD‐PLUS), and the test battery for attentional performance (TAP) as a well‐established assessment of attentional functions in the German‐speaking part of Europe.
Results
Sixty‐four patients with Neuro‐Sjögren, who were treated at our university hospital between December 2016 and January 2019, were included. Evidence for the presence of cognitive impairment was found in 55% of patients with Neuro‐Sjögren. The degree of cognitive impairment ranged from mild (38%) to severe (17%). Attentional and mnemonic subtests showed pronounced cognitive impairment in patients with Neuro‐Sjögren.
Interpretation
Our results suggest that a substantial proportion of patients with Neuro‐Sjögren suffer from cognitive impairment, putatively as a corollary of attentional deficits, which might exert adverse effects on occupational abilities, other cognitive functions, and social role functioning.
Despite a vast amount of data generated by proteomic analysis on cochlear fluid, novel clinically applicable biomarkers of inner ear diseases have not been identified hitherto. The aim of the present ...study was to analyze the proteome of human perilymph from cochlear implant patients, thereby identifying putative changes of the composition of the cochlear fluid perilymph due to specific diseases. Sampling of human perilymph was performed during cochlear implantation from patients with clinically or radiologically defined inner ear diseases like enlarged vestibular aqueduct (EVA; n = 14), otosclerosis (n = 10), and Ménière’s disease (n = 12). Individual proteins were identified by a shotgun proteomics approach and data-dependent acquisition, thereby revealing 895 different proteins in all samples. Based on quantification values, a disease-specific protein distribution in the perilymph was demonstrated. The proteins short-chain dehydrogenase/reductase family 9C member 7 and esterase D were detected in nearly all samples of Ménière’s disease patients, but not in samples of patients suffering from EVA and otosclerosis. The presence of both proteins in the inner ear tissue of adult mice and neonatal rats was validated by immunohistochemistry. Whether these proteins have the potential for a biomarker in the perilymph of Ménière’s disease patients remains to be elucidated.
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