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[Benign paroxysmal positional vertigo and provocative maneuvers].

Main features of the benign paroxysmal positional vertigo (B.P.P.V.) are: latency before the onset of vertigo, nystagmus of the rotatory type beating toward the lower ear, nystagmus tires out, nystagmus gets inverted when the head is brought back to orthostatism, nystagmus is reproducible as many times as the position is taken. B.P.P.V. is due to a deposit of heavy material on the cupula of the posterior semi circular canal. In this unusual condition, the cupula moves under the effect of gravity acceleration. The goal of the treatment is to free the cupula. The manoeuvre consists after determination of the position that elicits the vertigo to move the whole head and body together of the patient to a 180 degree opposite position in which the addition to the endolymph flow forces and weight forces of the material will unstick it from the cupula. The positive result of the manoeuvre is instantly proved by the arising of a rotatory nystagmus beating again toward the sick ear. In other words it is not the inversion of the primary nystagmus but a nystagmus beating the same direction. This is explained by the dynamic of the cupula: in the prime position the density modified cupula moves toward the canal. At the end of the manoeuvre when the velocity of the head is zero, the cupula has to support different forces. First the addition of the endolymph flow forces and the inertia of the heavy material makes the cupula move toward the ampulla. Secondly when the superficial tension forces are too high the heavy material unstick from the cupula and it goes back to its normal position. En this very moment the cupula moves toward the canal. The results are of more than 90% positive in one ore two sessions 4,2% of recurrence. The manoeuvre is unsuccessful in spontaneous nystagmus revealed by a position, in torsional nystagmus as in fistulas or in central position nystagmus.

Humans↗

Perfusion of the inner ear with streptomycin.

Any medical or surgical treatment of Meniere's disease is always suspect because the natural history is so variable and the pathologic physiology is not well-known. Even the occurrence rate in one and both ears is not known. It is certainly true that endolymphatic hydrops, caused by the failure of absorption of endolymph in the endolymphatic sac, is the principal pathology in the classical, fully developed Meniere's disease. While the endolymphatic shunt operation is correct in theory, in most ears, it does not work because the surgeon does not always locate the lumen of the sac and when located, the shunt tube does not remain open. While vestibular neurectomy is more likely to give permanent relief of vertigo as compared to the endolymphatic sac operation, the operation is difficult and dangerous and does nothing for the hearing. The vestibulotoxic action of the aminoglycocide antibiotics, especially streptomycin, when introduced into the perilymph of the lateral semicircular canal will destroy the vestibular receptors without making the hearing worse, and by acting on the dark cells, reduce the production of endolymph. Perfusion of the perilymph with streptomycin through an opening in the bony lateral semicircular canal is the operation of choice for Meniere's disease, benign paroxysmal postural vertigo and other forms of vertigo. So far 66 such operations have been done during the last three years with very encouraging results.

Aged↗

The membrane rupture theory of Menière's disease--is it valid?

The Membrane Rupture Theory states that the acute attack of Menière's disease occurs when endolymph, with its high potassium ion concentration, escapes into the perilymph and surrounds the first-order neuron. Initially, this causes partial depolarization of the nerve and an increased resting discharge, followed by complete depolarization. Clinically, one would expect an initial irritative nystagmus (toward the affected side) followed by a paralytic nystagmus (toward the unaffected side). To confirm this, the guinea pig perilymphatic space was perfused with an artificial endolymph solution. The results confirmed an irritative/paralytic sequence of nystagmus that differs from the pattern of spontaneous nystagmus observed with ENG monitoring during the acute attack of Menière's disease. Early in the attack, one observes a paralytic nystagmus followed by a secondary nystagmus beating toward the affected side (similar to an irritative nystagmus) as the patient recovers. This raises questions about the validity of the Membrane Rupture Theory.

Animals↗

Effect of peroral glycerol administration on inner ear fluid electrolytes of guinea pigs.

After the oral administration of 50% glycerol (12 mL/kg), serum, CSF and inner ear fluids from scala tympani perilymph, scala vestibuli perilymph, and scala media endolymph were collected from normal guinea pigs under sodium pentobarbital anesthesia (25-35 mg/kg). The sodium and potassium concentrations were determined by microflame photometry. Increases in sodium concentrations were found in CSF, scala tympani perilymph, scala vestibuli perilymph, and cochlear endolymph. No significant change was observed in the serum. These sodium increases were considered to be due to the dehydration caused by the osmotic action of glycerol. Potassium concentration was increased only in scala tympani perilymph. Oral administration of glycerol was found to be more gradual and effective in dehydration compared to intravenous injection.

Administration, Oral↗

Clinical implications of experiments on alteration of the labyrinthine fluid pressures.

Hearing is affected by changes in hydrostatic pressure of the perilymph, but very high pressures are required to produce a significant loss. Among the observed findings in cats are a rapidly reversible decrease in the sensitivity of the cochlear microphonic that is greater for low frequencies, harmonic distortion and reduction of dynamic range as measured by the input-output function for the cochlear microphonic, and a change in the summating potential from negative to positive. These changes are attributed to a temporary reduction in the size of the cochlear duct due to a shift of water molecules out of the cochlear duct into the blood until the resulting increase in osmotic pressure balances the increase in hydrostatic pressure. Consequently, the organ of Corti is biased "upward" away from the scala tympani. Increasing the hydrostatic pressure of the endolymph produces a "downward" biasing of the organ of Corti and has an opposite effect upon the summating potential. Presumably this is what happens in Meniere's disease. Because of the presence of the perilymphatic canaliculi, the locus of the hydrostatic pressure effect is assumed to be in the region of the reticular lamina. A theory has been developed to explain why cochlear function is very sensitive to relative differences between the hydrostatic pressures of the perilymph and the endolymph but is resistant to large variations in the absolute magnitudes of those pressures. Some of the clinical implications of this theory are discussed.

Animals↗

[Prognostic value of hormonal and immunological indices in the combined treatment of esophageal cancer].

A combination therapy consisting of two endolymphic infusions of BCG vaccine and methotrexate followed by remote gamma therapy 10 days after the second infusion was given to 96 patients with stage III esophageal tumors. Complete response was observed in 64.4 and partial--in 33.3% of cases. An evaluation of response carried out on the basis of 40 hormonal and immunological indices showed that immunological factors make the major contribution to antitumor resistance. The report contains a table of parameters which provide information indispensable for the prognosis of treatment depending on the response of internal environment to endolymphic infusion.

Adult↗

Scanning electron microscopic observation of dark cells after streptomycin perfusion of the vestibule in guinea pigs.

Hearing has been stabilized in the majority of patients studied in the treatment of Meniére's disease with streptomycin. This observation suggests that effects of streptomycin may ameliorate endolymphatic hydrops, possibly by attenuating the activity of secretory tissue. The purpose of this study is to observe the dark cells of the utricle in guinea pigs after streptomycin perfusion of the vestibule. Twelve pigmented guinea pigs weighing 250-350 grams were used in this study. The vestibules in five guinea pigs were perfused monolaterally with 150 micrograms of streptomycin in artificial perilymph and, in seven, the vestibules were perfused only with artificial perilymph as a control group. Specimens were processed for observation with a scanning electron microscope. After streptomycin perfusion, the margin of the dark cells became indistinct. The luminal surface of the cells bulged out like a dome. The microvilli decreased or were absent, and some debris was deposited on the surface. In four of the five animals, the luminal membrane of the dark cell ruptured. The cytoplasm and organelle extruded into the endolymphatic space. After the cellular debris moved out into the endolymph, either a vanished cell or a nucleus in an empty nest was observed. These cells appeared damaged and destroyed. The results indicate that the dark cells in the membranous wall of the utricle were affected by streptomycin. The results lead to the assumption that streptomycin may reduce the volume of endolymph by damaging the dark cells of the utricle.

Animals↗

Lipocortin I immunolocalization in normal and hydropic guinea pig ears.

Annexins are a family of eight highly conserved proteins that bind phospholipids in the presence of calcium. One of these proteins, lipocortin I, has restricted distribution in adult and developing tissues, suggesting regulatory function. Among the protean roles theorized are regulation of inflammation by influencing eicosanoid production, participation in endo- and exocytosis, and control of membrane permeability. Such processes could have important roles in the inner ear; therefore, we investigated the patterns of lipocortin I expression in the normal guinea pig ear. Lipocortin I appeared at high levels in nonsensory, endolymph-facing tissues. Perilymph-facing cells had little lipocortin I activity. Lipocortin I was minimally expressed, or is absent, in sensory cells of the cochlea and vestibular systems. In the kidney, changes in quantity and distribution of lipocortin I have been seen during recovery from acute tubular necrosis. In an attempt to gain insight into the role of lipocortin I, the authors investigated its response to an experimental insult. Surgically created endolymphatic hydrops was chosen as an insult involving the endolymph-producing epithelia that richly express lipocortin I. Comparing unilaterally created hydrops, for up to 3 weeks' duration, to contralateral control ears demonstrated no quantitative or distribution changes in lipocortin I.

Animals↗

Laboratory experience with experimental endolymphatic hydrops.

Experimental endolymphatic hydrops refers to the creation of hydrops in the experimental animal and represents a histologic correlate for Meniere's disease. Details of the surgical means to create this condition in guinea pigs are provided. Alterations in endolymph fluid composition and relative endolymph pressure occur with hydrops. Deterioration in auditory and vestibular function secondary to hydrops can develop.

Animals↗

[Experimental study of streptomycin on 45Ca intake of otolithic membranes].

45CaCO3 was injected into guinea pigs, and the radioactivity in otolithic membranes of utriculi and sacculi, auditory ossicles and femora was determined by liquid scintillation spectrometry, to study the dynamic effect of streptomycin on calcium content of otolithic membranes, as a means to explore the mechanism of streptomycin ototoxicity. The results showed that otoconium was a dynamic structure which took up 45Ca in a time course generally comparable to that of bone. Saccular otolithic membranes showed greater intake than utricular membranes. The calcium ion concentration of saccular endolymph was greater than that of the utriculus and the two maculas were not identical. Streptomycin may influence 45Ca uptake in the two macular otolithic membranes, causes calcium metabolic disorder and a fall of otolithic calcium content. It is possible that the fluid environments of the endolymph have changed, therefore dysfunction of otolithic organ may occur. This hypothesis may be one of the explanation of the mechanism of streptomycin ototoxicity.

Animals↗

Ménière disease caused by an anomalous vein of the vestibular aqueduct.

The precise cause of Ménière disease remains unclear. Multiple causes have been proposed with most experimental evidence pointing to impaired fluid resorption by the endolymphatic duct and sac as the final common pathway in development of hydrops. We report a unique case of Ménière disease secondary to compression of the endolymphatic duct and sac by an anomalous vein of the vestibular aqueduct. The resulting mechanical obstruction led to excessive accumulation of endolymph with clinical signs of Ménière disease. We review the literature and discuss proposed pathogenesis of disease. The finding of this anomalous vein provides further evidence that anatomical obstruction of the endolymphatic duct and sac may lead to Ménière-like symptoms. This unique example of an anatomical variant offers additional insight into the pathophysiology of endolymphatic hydrops.

Endolymph↗

Distribution of labeled chloroquine in the inner ear.

Autoradiography of the inner ear was performed at varying intervals following intravenous injection of either chloroquine tagged with carbon 14 (14C), or an iodine 125 (125l)-labeled analogue of chloroquine, in rats. In pigmented rats a strong accumulation and retention was noted in the melanin-bearing tissues. In the inner ear there was a very high concentration in the melanin-containing tissues, eg, the stria vascularis and the planum semilunatum. A strong retention was found in these structures 13 days after injection. Accumulation was not observed in the endolymph nor in the perilymph. No accumulation was found in the inner ear of an albino rat. The ototoxic effects of chloroquine may be caused by an accumulation of the drug in the melanin-containing structures in the inner ear, leading to pathological changes in these tissues and secondary lesions in the receptor cells.

Animals↗

Pathologic features of the inner ear in congenital deafness.

We present the morphologic findings of the temporal bones and brain of a patient with congenital deafness. We discuss these findings in relation to pathologic observations in other reported cases of congenital deafness. Morphologic abnormalities in the patient were mainly in the pars inferior of the membranous labyrinths. The osseous labyrinths were well developed. There was severe dilation of the cochlear duct with herniation of the Reissner membrane, extensive atrophy of the stria vascularis that was associated with calcified thrombi to the strial vessels, encasement of the tectorial membrane in a syncytium, and dyspiastic or regressive degeneration of the organ of Corti. Absence of spiral ganglion cells and their fibers was a prominent feature. The extensive and varied pathologic changes that were present in our patient simultaneously suggest a congenital abnormality in endolymph production and raise the possibility of anomalous development of the labyrinthine vasculature.

Aged↗

Unidirectional inner ear valve implant for endolymphatic sac surgery in Meniere's disease.

In five patients with long-standing Meniere's disease, a unidirectional inner ear valve was implanted into the endolymphatic sac (ELS) to facilitate removal of excess endolymph in the hydropic state. These patients were all candidates for ablative surgery. They all had intractable vertigo and severe hearing losses. Four out of five patients had positive preoperative glycerol tests. In the patients with positive glycerol tests, the group averages before surgery were as follows: pure-tone average (PTA), 63 dB; speech reception threshold (SRT), 79 dB; and discrimination score, 27%. All of the patients, except a patient with a negative glycerol test, benefited from the surgery, including exceptional hearing improvements, averages of 21 dB in PTA, 30.5 dB in SRT, and 48% in discrimination, which remained so for at least a one-year minimum follow-up. All patients with preoperative positive glycerol tests had a class A result according to the criteria set forth by the American Academy of Ophthalmology and Otolaryngology. The cumulative follow-up exceeded the minimal requirements by a factor of 39 times. The only failure was in a patient with a negative glycerol test, which was predictable. Results of tomography confirmed the correct position of the valve without evidence of migration or extrusion even in the failure. This new valve appears to be a safe and more effective implant than Silastic sheeting alone or any other ELS implant in patients with a positive glycerol test.

Adult↗

Experimental endolymphatic hydrops in the rat.

In the rat, the epithelial lining of the endolymphatic duct and sac, and the contents of the sac, showed remarkable differences in comparison with these structures in the guinea pig and man. Obliteration of the endolymphatic duct resulted in endolymphatic hydrops of varying severity in 55% of the rats, after survival times varying from one to five months. The presence of a positive periodic acid-Schiff-stain for coagulum accumulating in the endolymphatic duct after prolonged saccus obliteration suggests active involvement of the endolymphatic duct in the migration of endolymph toward the endolymphatic sac.

Animals↗

Principles in cochlear toxicity.

The hair cells of the cochlea (neuroepithelium) represent the primary target in most drug-induced ototoxic adverse effects on hearing (e.g. aminoglycoside antibiotics). To what extent an exogenically-induced morphologic damage to hair cells is reversible is not known. In aging structurally altered hair cells can persist for years likewisely not any longer participating in sensory transduction as the hair cells degenerate, secondary changes occur in the spiral ganglion cells and the neuronal pathways. Following heavy metal poisoning an adverse effect is observed on both central and peripheral innervation of the cochlea and only minor primary changes occur in the receptor cells. The link between function and morphology in the cochlea is very obvious regarding the high and middle frequencies with a distinct tonotopic localisation whereas for low frequencies (below 1 khz) such a specific morphologic correlation is lacking. Ototoxic effects primarily affecting the source for the production of endolymph, i.e. the stria vascularis, become manifest at all frequencies and at a rather early stage. Independent of type of substance penetrating into the inner ear, the substance has a considerably slower elimination rate as compared with all other compartments in the body. The toxicity of the drugs seems to be more related to its tissue binding capacity and saturation of receptor sites than related to the concentration of the drug in endo-or perilymph.

Age Factors↗

In situ real-time sequential potentiometric determinations of potassium concentrations from three cochlear regions in noise-exposed rats.

Double-barrelled potassium selective microelectrodes (K-ISME) were used in situ for real-time sequential determinations of potassium concentrations (CK+) in endolymph, marginal cells and the spiral ligaments of rats exposed to moderate noise at 100 dB for 30 min (NE) and control (CTL) animals. CK+ in NE animals at these sites did not differ significantly when compared to CK+ in CTL animals. However, there was a slight decrease in CK+ in marginal cells in the noise-exposed animals.

Animals↗

The Epley maneuver for the treatment of benign paroxysmal positional vertigo.

In recent years, different forms of physical therapy have been proposed for the treatment of benign paroxysmal positional vertigo (BPPV). These mainly consist of maneuvers aiming to reposition and disperse free-floating endolymph particles in the posterior semicircular canal. We report our experience with one of these procedures, the Epley maneuver (EM), in treating 30 cases of BPPV. Twenty-six patients (87%) were cured, while four (13%) did not respond to treatment. These results are similar to those reported in the literature for the EM and the Semont maneuver.

Adult↗