Olaf Michel

Hearing Loss as a Sequel of Lumbar Puncture

Only a few case reports have been published about hearing impairment following lumbar puncture, and not all were thoroughly documented by audiograms. We present nine cases of hearing loss following myelography, lumbar puncture, and spinal anesthesia. We speculate that this rare complication arises only in persons with a wholly or partially patent cochlear aqueduct, and occurs via the release of perilymphatic fluid in the cerebrospinal space. Hearing loss was seen in eight of the nine patients in the lower frequencies, and in six of the nine patients on both sides. Recovery to normal hearing was noticed in six of the nine patients. Transient hearing loss may occur more often than it is generally assumed, and the symptom can remain unnoticed. Since not all of these hearing losses proved to be fully reversible, we suggest informing patients about this complication for medicolegal reasons.

Effect of irrigation of the nose with isotonic salt solution on adult patients with chronic paranasal sinus disease.

Abstract In a prospective, randomized, controlled, double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease. Subjects (n = 40) were randomly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution. The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required. Nasal endoscopy, plain radiography of the paranasal sinuses, olfactometry, anterior rhinomanometry, and a saccharin-clearance test were carried out on days 1 and 7. Patients recorded rating scales of general discomfort, nasal airway obstruction, agreeableness of the irrigation, duration of improved nasal resistance after each irrigation, and the amount of additional nasal spray in a diary. Nasal air flow was not improved significantly. Subjective complaints, endonasal endoscopy, and radiography results revealed a significant improvement in both groups (P = 0.0001). In comparison, the two groups were not significantly different in outcome. Endonasal irrigations with salt solutions are effective in the treatment of chronic sinusitis, and a significant difference between Ems salt and sodium chloride was not observed.

Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochlea of guinea pigs after intratympanical endotoxin-treatment.

Since NO is believed to be involved in cochlear physiology, presence of the constitutive isoforms of nitric oxide synthase (NOS), and the target enzyme of NO, soluble guanylyl cyclase (sGC) in structures of the mammalian cochlea have been demonstrated. To date, no reports have been published regarding the detection of the inducible isoform (NOS II) in the cochlea. In order to show the capability of iNOS expression in cochlear tissue, a mixture of proinflammatory bacterial lipopolysaccharides (LPS) and tumor necrosis factor alpha (TNF-alpha) was injected into the tympanic cavity of guinea pigs, vs. saline-solution as control. Paraffin sections of LPS/TNF-alpha treated and saline-treated cochleae (6 h) were examined immunohistochemically with specific antibodies to neuronal, endothelial and inducible NOS and to sGC. Initiated expression of iNOS in the cochlea was observed in the wall of blood vessels of the spiral ligament (SL) and the modiolus, in supporting cells of the organ of Corti, in the limbus, in nerve fibers and in a part of the perikarya of the spiral ganglion after LPS/TNFalpha-treatment. iNOS was not detected in saline-treated control tissue. Expression of both constitutive NOS-isoforms (endothelial and neuronal NOS) and of sGC showed no significant differences in both experimental groups. Endothelial eNOS and neuronal bNOS were detected co-localized in ganglion cells, in nerve fibers, in cells of the SL and in supporting cells of the organ of Corti, but not in sensory cells. Strong labeling for bNOS became evident in the endosteum of the cochlea, while in the endothelium of blood vessels and in the epithelium of the limbus only eNOS could be labeled. sGC could be detected in SL, in supporting and sensory cells of the organ of Corti, in nerve fibers, ganglion cells, in the wall of blood vessels and in the limbus-epithelium. While small amounts of NO, generated by bNOS and eNOS, seem to support the cochlear blood flow and auditory function as well as neurotransmission, high amounts of iNOS-generated NO could have dysregulative and neurotoxic effects on the inner ear during bacterial and viral infections of the middle and inner ear.

Nitric oxide synthase inhibitor suppresses the ototoxic side effect of cisplatin in guinea pigs.

Cisplatin is known to cause inner ear damage (ototoxicity). The role of inducible nitric oxide synthase (iNOS) in the cochlea of guinea pigs after injections of cisplatin or a combination of cisplatin and NOS inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) i.p. was examined electro- and immunohistochemically. The auditory brain stem responses (ABR) were measured prior to injection and 3 days after the injection. Three days after injection, the cochleas were examined immunohistochemically for iNOS. We found that iNOS was expressed in the cisplatin- and L-NAME/cisplatin-treated cochlea. The threshold shift of ABR was significant in the cisplatin group, whereas it was decreased in the L-NAME/cisplatin group. iNOS catalyzed high NO levels lead to inner ear dysfunction. Our results indicate that iNOS mediates the ototoxicity of cisplatin.

Nitric oxide synthase in the vestibulocochlear system of mice

The exact distribution of nitric oxide-synthases (NOS) and the NO-target enzyme soluble guanylyl cyclase (sGC) in the cochlea and vestibular organ is an issue of current discussion. The existence of NOS-isoforms in the cochlea of the guinea pig has been described recently, while information about the vestibular system are still rare and non-satisfying. In order to gain more information, immunostaining was performed, using specific antibodies to NOS I-III and to sGC, on paraffin sections of complete temporal bones from mice. NOS III could be detected in cochlea and vestibular ganglion cells, in nerve fibres, in outer hair cells of the cochlear and in the sensory epithelium of the maculae. Also, the spiral ligament and the limbus epithelium was positive to NOS III. NOS I was found in the sensory epithelium of the maculae and cristae ampullares, outer and inner hair cells of the cochlea, in nerve fibres and in ganglion cells. In contrast to that NOS II could not be detected at all. Furthermore, a strong NOS I immunoreaction was displayed on the endosteum of the bone, while the periosteum was lacking of NOS. NOS detection was accompanied by immunoreactivity to sGC. The findings imply that NOS I and III-generated NO is involved in neurotransmission and other regulative processes in the vestibulocochlear system.

Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa

Abstract. The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps (n=11) and controls of human mucosa of the normal middle turbinates (n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.

Permeabilität der runden Fenstermembran für Prednisolon-21-Hydrogensuccinat Prednisolongehalt der Perilymphe nach lokaler Applikation vs. systemischer Injektion

ZusammenfassungHintergrund und Fragestellung. Zur Behandlung vestibulokochleärer Störungen gehört systemisch appliziertes Prednisolon zur Therapie der Wahl. Die in den Labyrinthflüssigkeiten zu erreichenden Konzentrationen sind wegen unerwünschter Nebenwirkungen limitiert. Eine direkte Applikation im Bereich der runden Fenstermembran könnte höhere therapeutische Wirkspiegel im Erfolgsorgan erzielen. Ziel der Studie war daher die Bestimmung der Permeabilität der runden Fenstermembran beim Meerschweinchen nach lokal appliziertem Prednisolon. Methodik. Die Applikation von Prednisolon-21-Hydrogensuccinat (5 mg in 0,1 ml) erfolgte unmittelbar in die runde Fensternische auf die Fenstermembran. Als Vergleich dienten Perilymphproben nach intraperitonealer Applikation von 60 mg/kg KG Prednisolon-21-Hydrogensuccinat. Perilymphproben wurden jeweils nach 15, 20, 80, 180, 330 und 960 min (n=60) nach Präparation der Kochlea und Eröffnung der Apex cochleae entnommen. Der Prednisolonspiegel in den Perilymphproben wurde durch eine isokratische Hochdruckflüssigkeitschromatographie (HPLC) quantitativ bestimmt. Ergebnisse. Die höchste Prednisolonkonzentration mit 952,3 (±382,7) mg/l fand sich 180 min nach lokaler Applikation. Nach 960 min betrug die Konzentration 18,7 (±16,9) mg/l. Nach systemischer Applikation wurden Konzentrationen von maximal 14,7 (±7,1) mg/l gemessen. Schlussfolgerung. Durch eine einmalige, lokale Applikation werden hohe Konzentrationen von Prednisolon in kochleärer Perilymphe erzielt. Messbare Prednisolonkonzentrationen fanden sich bis zu 16 h nach einmaliger Applikation.AbstractBackground and objective. Prednisolone is the drug of first choice for the treatment of cochleovestibular disorders, such as sudden hearing loss. Because of the known side effects, the efficient drug levels to be achieved within inner ear fluids are limited by intravenous administration. The aim of the study was to determine the concentration in the perilymph of prednisolone-21-hydrogen succinate applied into the round window niche in comparison to the concentration after intraperitoneal application. Methods. Application of prednisolone-21-hydrogen succinate (5 mg in 0.1 ml) on the round window membrane was performed after sedation under microscopic view directly into the round window niche of the guinea pig. In order to compare the results, perilymph samples after systemic application of 60 mg/kg body weight prednisolone were used. The time between application and taking specimens of perilymph from the cochlea varied. Specimens of perilymph were obtained after 15, 20, 80, 180, 330, and 960 min (10 specimens in each group, n=60) by dissecting the cochlea and opening the apex cochleae. Levels of prednisolone-21-hydrogen succinate in perilymph were measured by isocratic high-pressure liquid chromatography (HPLC). Results. The highest levels of prednisolone-21-hydrogen succinate were found after 180 min: 952.3 mg/l (95% confidence interval: 382.7). After 960 min the level was 18.72 mg/l (95% confidence interval: 16.9). In the group with systemic application, the levels measured were below 14.71 mg/l (95% confidence interval: 7.05). Conclusion. The results demonstrate that high levels of prednisolone-21-hydrogen succinate in perilymph are achievable by local application of a single dose into the round window niche. After application of 5 mg, the levels of prednisolone are measurable up to 16 h.

Localization of the NO/cGMP-pathway in the cochlea of guinea pigs.

The presence of nitric oxide synthase (NOS) in substructures of the cochlea of guinea pigs is an issue of current focus. Moreover, information concerning the localization of cells effected by the NO/cGMP-pathway are rare. Paraffin sections of guinea pig cochlea were incubated with specific antibodies to the three known NOS isoforms, soluble guanylyl cyclase (sGC) and cyclic guanosine-monophosphate (cGMP), the second messenger system of NO. While detection of inducible iNOS failed in all cochlear structures, expression of endothelial eNOS was found in the spiral ligament, in the stria vascularis, in cells of the organ of Corti, in nerve fibers and in some perikaryia of the spiral ganglion. The cochlear nerve showed an accentuated affinity for immunostaining in distal, basal segments of the cochlea. Neuronal bNOS was found predominantly in the endosteum of the modiolus and cochlea and was less intensively present in all perikaryia of the spiral ganglion and in the spiral ligament. Supporting cells of the organ of Corti and cells in the limbus spiralis displayed only modest immunostaining, while bNOS was not found in outer and inner hair cells. NOS detection was accompanied by immunoreactivity to sGC and to cGMP. The presence of NOS and its second messenger system gives evidence for a possible involvement in neurotransmission, regulation of the cochlear amplifier and in homeostasis.

Nitric oxide synthase inhibitor reduces the apoptotic change in the cisplatin-treated cochlea of guinea pigs.

Cisplatin is known to cause inner ear damage. The role of nitric oxide (NO) in the cochlea of the guinea pigs after injections of cisplatin or a combination of cisplatin and NO synthase (NOS) inhibitor [NG-nitro-L-arginine methyl ester (L-NAME)] i.p. was examined by means of immunohistochemistry. Three days after injection, the cochleas were examined immunohistochemically for single-stranded DNA (ssDNA). We found that ssDNA was expressed in the stria vascularis and spiral ganglion cells of the cisplatin-treated cochlea. In the L-NAME/cisplatin-treated cochlea, the number of cells that exhibited positive staining for ssDNA was markedly reduced. High NO levels lead to inner ear dysfunction under pathological conditions. Our results indicate that NO mediates the ototoxicity of cisplatin.

Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea.

The aim of this study was to investigate the involvement of oxidative stress and apoptosis in an animal model of Menieres disease. Endolymphatic hydrops (ELH) is generally accepted as the decisive histological characteristic of Menieres disease. Closure of the endolymphatic duct (Kimuras method) was used to induce endolymphatic hydrops in guinea pigs. Sham-operated animals served as controls. After 4 weeks the animals operated showed a significant elevation of the hearing thresholds as measured by audiometric brainstem responses (ABR) pre- and postoperatively. Immediately after the second ABR measurement, the animals were sacrificed for further immunohistological examinations of the inner ear with specific antibodies to active caspase-3 (cas-3) as a marker for apoptosis and antibodies to 8-isoprostane (8-iso) and nitrotyrosine (NT) as indicators of oxidative stress. Compared with the sham-operated controls, hydropic cochleae showed strong immunostaining for both oxidative stress markers in spiral ganglion cells, in the blood-vessels and fibrocytes of the lateral wall, as well as in supporting cells of the organ of Corti. Activation of cas-3 in spiral ganglion cells and the lateral wall was found exclusively in hydropic cochleae. Our findings suggest that oxidative stress is involved in the development of endolymphatic hydrops and may lead to cellular damage which induces apoptosis by activation of cas-3. Apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of Menieres disease.