Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high-dose aminoglycoside therapy.

Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25- to 8-kHz) and high-frequency (10- to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.

A computerized database of 'normal' auditory brainstem responses.

A computerized database of auditory brainstem responses (ABRs) from 'normal-hearing' volunteers is described. The database contains 'raw' responses recorded from 81 individuals; subjects varied in age from 20 to 56 years. The database is currently being used in a study to aid in the interpretation of ABRs for diagnostic purposes. Copies of the database are available over the world-wide web (http:¿¿www.engg.le.ac.uk¿abrdata).

Visual field defects associated with vigabatrin therapy.

OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.

Comparison of distortion product OAE generation between a patient group requiring frequent gentamicin therapy and control subjects.

Although the animal models used to characterize aminoglycoside ototoxicity are well developed, the initial stages of the ototoxic process of this important group of antibiotics in humans are less well understood. A group that receives frequent aminoglycoside therapy are cystic fibrosis (CF) patients, who may receive cumulative doses of gentamicin over 200 g in their lifetime. Consequently they represent a group in which it is particularly appropriate to monitor regularly auditory function. In this preliminary study, 15 young (aged 9-18 years) CF patients had their pure tone thresholds measured over 0.25-12 kHz. Their distortion product otoacoustic emission (DPOAE) growth functions were also measured at f2 = 2, 4 and 6 kHz with f2/f1 = 1.22. These results were compared with those obtained from 36 control volunteers of similar age. Fourteen of the CF patients had normal hearing (pure tone audiogram (PTA) thresholds < or = 10 dB HL over 0.25-8 kHz). In this group, there was a significant elevation of the stimulus levels required to generate a 2f1-f2 DPOAE < or = 10 dB SPL at 4 kHz. This elevation may represent one of the earliest changes in outer hair cell performance caused by gentamicin, although it may also be due to the CF condition itself. Whilst this measurement alone cannot be taken to indicate any serious cochlear dysfunction, it may have some clinical use as an early indicator or marker of functional deficit in the cochlea.

Topographic mapping of the pattern onset evoked magnetic response to stimulation of different portions of the visual field.

Visual evoked magnetic responses to pattern onset/offset stimuli were recorded in 5 normal subjects. The outgoing and ingoing magnetic currents were seen maximally over the contralateral visual cortex to the half field stimulated in the majority of subjects. The distribution of magnetic currents with half field stimulation would be consistent with a dipole on the midline with the positive end pointing laterally. Quadrantic stimuli produced dipoles which would be consistent with a vector sum of dipoles situated, in the case of upper quarter field stimulation, in the lingual gyri on the floor of the calcarine fissure. Lower quadrantic stimulation produced a vector consistent with dipoles on the cuneal gyrus and on the ceiling of the calcarine fissure producing a resultant vector. The use of paired octant stimuli to improve localisation was demonstrated on both right left and upper and lower half fields.

Chronotopographical analysis of the pattern onset visual evoked magnetic response (VEMR): implications for waveform peak identification.

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was studied in five normal subjects using a single channel BTi magnetometer. Topographic distributions were analysed at regular intervals following stimulus onset (chronotopography). Two distinct field distributions were observed with half field stimulation: (1) activity corresponding to the C11 m which remains stable for an average of 34 msec and (2) activity corresponding to the C111 m which remains stable for about 50 msec. However, the full field topography of the largest peak within the first 130 msec does not have a predictable latency or topography in different subjects. The data suggest that the appearance of this peak is dependent on the amplitude, latency and duration of the half field C11 m peaks and the efficiency of half field summation. Hence, topographic mapping is essential to correctly identify the C11 m peak in a full field response as waveform morphology, peak latency and polarity are not reliable indicators.

Topographic mapping and source localization of the pattern onset visual evoked magnetic response.

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was investigated using 4 check sizes and 3 contrast levels. The pattern onset response consists of three early components within the first 200ms, CIm, CIIm and CIIIm. The CIIm is usually of high amplitude and is very consistent in latency within a subject. Half field (HF) stimuli produce their strongest response over the contralateral hemisphere; the RHF stimulus exhibiting a lower positivity (outgoing field) and an upper negativity (ingoing field), rotated towards the midline. LHF stimulation produced the opposite response, a lower negative and an upper positive. Larger check sizes produce a single area of ingoing and outgoing field while smaller checks produce on area of ingoing and outgoing field over each hemisphere. Latency did not appear to vary with change in contrast but amplitudes increased with increasing contrast. A more detailed topographic study incorporating source localisation procedures suggested a source for CIIm-4cm below the scalp, close to the midline with current flowing towards the lateral surface. Similar depth and position estimates but with opposite polarity were obtained for the pattern shift P100m previously. Hence, the P100m and the CIIm may originate in similar areas of visual cortex but reveal different aspects of visual processing.