Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.

Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls (P = 0.001); half were previously unknown (AF < 0.000002). MYO6, MYO7A, PTPRQ, and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1N321I/+ mice, carrying the TMC1:p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.

FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases.

Hearing loss and visual impairment in childhood have mostly genetic origins, some of them being related to sensorial neuronal defects. Here, we report on eight subjects from four independent families affected by auditory neuropathy and optic atrophy. Whole-exome sequencing revealed biallelic mutations in FDXR in affected subjects of each family. FDXR encodes the mitochondrial ferredoxin reductase, the sole human ferredoxin reductase implicated in the biosynthesis of iron-sulfur clusters (ISCs) and in heme formation. ISC proteins are involved in enzymatic catalysis, gene expression, and DNA replication and repair. We observed deregulated iron homeostasis in FDXR mutant fibroblasts and indirect evidence of mitochondrial iron overload. Functional complementation in a yeast strain in which ARH1, the human FDXR ortholog, was deleted established the pathogenicity of these mutations. These data highlight the wide clinical heterogeneity of mitochondrial disorders related to ISC synthesis.

Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission.

Dominant optic atrophy is a blinding disease due to the degeneration of the retinal ganglion cells, the axons of which form the optic nerves. In most cases, the disease is caused by mutations in OPA1, a gene encoding a mitochondrial large GTPase involved in cristae structure and mitochondrial network fusion. Using exome sequencing, we identified dominant mutations in DNM1L on chromosome 12p11.21 in three large families with isolated optic atrophy, including the two families that defined the OPA5 locus on chromosome 19q12.1-13.1, the existence of which is denied by the present study. Analyses of patient fibroblasts revealed physiological abundance and homo-polymerization of DNM1L, forming aggregates in the cytoplasm and on highly tubulated mitochondrial network, whereas neither structural difference of the peroxisome network, nor alteration of the respiratory machinery was noticed. Fluorescence microscopy of wild-type mouse retina disclosed a strong DNM1L expression in the ganglion cell layer and axons, and comparison between 3-month-old wild-type and Dnm1l+/- mice revealed increased mitochondrial length in retinal ganglion cell soma and axon, but no degeneration. Thus, our results disclose that in addition to OPA1, OPA3, MFN2, AFG3L2 and SPG7, dominant mutations in DNM1L jeopardize the integrity of the optic nerve, suggesting that alterations of the opposing forces governing mitochondrial fusion and fission, similarly affect retinal ganglion cell survival.

Predictive factors of cochlear implant outcomes in the elderly.

OBJECTIVE: To analyze predictive factors of cochlear implant outcomes and postoperative complications in the elderly. STUDY DESIGN: Prospective, longitudinal study performed in 10 tertiary referral centers. METHODS: Ninety-four patients aged 65-85 years with a profound, postlingual hearing loss were evaluated before implantation, at time of activation, and 6 and 12 months after cochlear implantation. Speech perception and lipreading were measured using disyllabic word recognition in quiet and noise, and lipreading using disyllabic words and sentences. The influence of preoperative factors on speech perception in quiet and noise at 12 months was tested in a multivariate analysis. Complications, presence of tinnitus and of vestibular symptoms were collected at each evaluation. RESULTS: The effect of age was observed only in difficult noisy conditions at SNR 0 dB. Lipreading ability for words and sentences was negatively correlated with speech perception in quiet and noise. Better speech perception scores were observed in patients with shorter duration of hearing deprivation, persistence of residual hearing for the low frequencies, the use of a hearing aid before implantation, the absence of cardiovascular risk factors, and in those with implantation in the right ear. General and surgical complications were very rare, and the percentage of vestibular symptoms remained stable over time. CONCLUSION: This study demonstrates that cochlear implantation in the elderly is a well-tolerated procedure and an effective method to improve communication ability. Advanced age has a low effect on cochlear implant outcome. Analyses of predictive factors in this population provide a convincing argument to recommend treatment with cochlear implantation as early as possible in elderly patients with confirmed diagnosis of a severe-to-profound hearing loss and with only limited benefit from hearing aid use in one ear.

Brain voice processing with bilateral cochlear implants: a positron emission tomography study.

Most cochlear implantations are unilateral. To explore the benefits of a binaural cochlear implant, we used water-labelled oxygen-15 positron emission tomography. Relative cerebral blood flow was measured in a binaural implant group (n = 11), while the subjects were passively listening to human voice sounds, environmental sounds non-voice or silence. Binaural auditory stimulation in the cochlear implant group bilaterally activated the temporal voice areas, whereas monaural cochlear implant stimulation only activated the left temporal voice area. Direct comparison of the binaural and the monaural cochlear implant stimulation condition revealed an additional right temporal activation during voice processing in the binaural condition and the activation of a right fronto-parietal cortical network during sound processing that has been implicated in attention. These findings provide evidence that a bilateral cochlear implant stimulation enhanced the spectral cues associated with sound perception and improved brain processing of voice stimuli in the right temporal region when compared to a monaural cochlear implant stimulation. Moreover, the recruitment of sensory attention resources in a right fronto-parietal network allowed patients with bilateral cochlear implant stimulation to enhance their sound discrimination, whereas the same patients with only one cochlear implant stimulation had more auditory perception difficulties.

Vestibular disorders following BNT162b2 mRNA COVID-19 vaccination: A retrospective case series.

BACKGROUND: There are few publications regarding manifestations of vestibular disorders (VDs) following BNT162b2 mRNA COVID-19 vaccination. PURPOSE: We describe cases of VD potentially related to BNT162b2 vaccination and calculate its reporting rate, in order to enlarge knowledge about this adverse effect. METHODS: A retrospective analysis of cases of VD following BNT162b2 vaccination reported to the pharmacovigilance centre of Georges-Pompidou European Hospital (France), in 2021 was performed. In order to identify these cases from the pharmacovigilance database containing all our registered cases, we used the Standardised MedDRA Query (SMQ) 'vestibular disorders'. Then we analysed cases with vestibular symptoms, based on the association of typical manifestations. The reporting rate was calculated based on the number of VD cases and the number of vaccinated patients. RESULTS: Among 6608 cases reported to our centre related to COVID-19 vaccines during 2021, 34 VDs associated with BNT162b2 administration were included. They were mainly reported in females (79%), 62% occurred after the first dose and 32% were serious. Symptoms had completely resolved in 13 cases (38%). Vertigo was the most common symptom followed by balance disorders. Three patients received second dose without reappearance of VD. The final diagnosis was reported in 10 patients (six cases of vestibular neuritis, two cases of central VD, two cases of benign paroxysmal positional vertigo). The regional reporting rate was 26 [95% CI: 17-34] cases of VD per 1 million persons vaccinated. CONCLUSION: Although the relationship between vaccination and VD cannot be established, clinicians should be aware of this rare adverse effect.

New cochlear implant technologies improve performance in post-meningitic deaf patients.

The objective of the study was to compare the performance of cochlear implantation between post-meningitic and non-meningitic patients, and to evaluate the impact on hearing outcome of technical advances in cochlear implant technology. Retrospective chart review was used as the study design. Twenty adults with post-meningitic profound hearing loss receiving unilateral or bilateral cochlear implants between 1990 and 2008 were tested. Results were compared to a control group of 46 adults implanted for a non-meningitic hearing loss, with the same pre-operative speech scores. Speech scores were poorer in post-meningitic patients compared to those of control group, whatever the duration after implantation (p < 0.0001). Speech scores of subjects implanted and fitted before 2001 were compared to those of subjects implanted after 2001, with the same duration of hearing loss. Performance improved with implants and processors available after 2001, with a magnitude of improvement higher in post-meningitic patients (p < 0.0001 and p < 0.05 in post-meningitic and control groups, respectively, two-way ANOVA). Consequently, speech scores of post-meningitic patients implanted after 2001 achieved those of control subjects (two-way ANOVA). Advances in cochlear implant technology and coding strategy improve hearing outcome in post-meningitic adult patients, who now achieve similar performance as those of non-meningitic patients.

MRI characteristics of intralabyrinthine schwannoma on post-contrast 4 h-delayed 3D-FLAIR imaging.

PURPOSE: The purpose of this study was to describe the MRI characteristics of intralabyrinthine schwannoma (ILS) on post contrast three-dimensional (3D) fluid-attenuation-inversion-recovery (FLAIR) images obtained four hours after intravenous administration of a gadolinium-based contrast agent (4h-3D-FLAIR). MATERIALS AND METHODS: This IRB-approved retrospective multi-center study included patients presenting with typical ILS from January 2016 to October 2020. All medical charts were systematically collected. All MRI examinations, including 4h-3D-FLAIR images, were reviewed by two board-certified neuroradiologists. Main outcome measures were location, signal intensity and associated anomalies of ILS. RESULTS: Twenty-seven out of 8730 patients (0.31%) referred for the investigation of a cochleovestibular disorder had a final diagnosis of ILS. There were 13 men and 14 women with a mean age of 52 ± 17 (SD) years (age range: 20-86 years). The most common clinical presentation was unilateral progressive sensorineural hearing loss (16/27; 59%). All ILS were unilateral and 15 (15/27; 55%) were intracochlear. All ILS presented as a hypointense filling defect within the labyrinth on T2-weighted images that enhanced on post-contrast T1-weighted images. On 4h-3D-FLAIR images, all ILS presented as a hypointense filling defect, associated with diffuse perilymphatic hyperintensity. Two patients (2/27; 7%) presented with ipsilateral endolymphatic hydrops. CONCLUSION: ILS displays consistent features on post-contrast 4h-3D-FLAIR images. ILS should not be confused with endolymphatic hydrops and requires a systematic analysis of the corresponding T2-weighted images.

Early complications and symptoms of cerebellopontine angle tumor surgery: a prospective analysis.

UNLABELLED: Our objective is to prospectively report very early complications and outcomes of cerebellopontine angle (CPA) surgery. Between January and August 2007, 72 patients were operated on by different transpetrosal approaches in a tertiary referral center. During preoperative assessment, facial nerve function (House-Brackmann grading system), the presence of vertigo or tinnitus and caloric test results were recorded and correlated with complications and symptoms occurring daily from day (D) 1 to D 8. The overall number of complications did not differ from those of former retrospective studies; nevertheless, the prospective feature of this study prompts several comments. Even slight (grade II) preoperative facial impairments increased the risk of severe postoperative facial dysfunction. Keratitis was frequent (42%) even in patients with normal facial function. Thrombo-embolic complications only occurred after long air-travel (≥5 h). Preoperative caloric test status was predictive of postoperative vestibular disturbance occurrence. With respect to the activity recovery; younger patients (<40 years old) displayed faster central compensations than the older (>60 years old) patients. This study highlights several features that may be used for preoperative patient counseling and complication management. In particular, the practitioner has to pay attention to even minor preoperative clinical signs of facial dysfunction to properly inform the patient of facial outcome. Routine ophthalmologic evaluation should be practiced, even when facial function is normal or subnormal. LEVEL OF EVIDENCE: 1b.

[The advantage of multidisciplinary treatment of presbycusis]. / Intérêt d'une prise en charge pluridisciplinaire de la presbyacousie.

Attributable to the ageing of the hearing system, presbycusis presents a wide variability in the general population. Early detection is necessary in order to be able to provide the patient with a suitable hearing aid. Collaboration between otolaryngologists and geriatricians proves to be advantageous as a consultation for a memory complaint may be the opportunity to detect presbycusis and vice versa.

Processing of voices in deafness rehabilitation by auditory brainstem implant.

The superior temporal sulcus (STS) is specifically involved in processing the human voice. Profound acquired deafness by post-meningitis ossified cochlea and by bilateral vestibular schwannoma in neurofibromatosis type 2 patients are two indications for auditory brainstem implantation (ABI). In order to objectively measure the cortical voice processing of a group of ABI patients, we studied the activation of the human temporal voice areas (TVA) by PET H(2)(15)O, performed in a group of implanted deaf adults (n=7) with more than two years of auditory brainstem implant experience, with an intelligibility score average of 17%+/-17 [mean+/-SD]. Relative cerebral blood flow (rCBF) was measured in the three following conditions: during silence, while passive listening to human voice, and to non-voice stimuli. Compared to silence, the activations induced by voice and non-voice stimuli were bilaterally located in the superior temporal regions. However, compared to non-voice stimuli, the voice stimuli did not induce specific supplementary activation of the TVA along the STS. The comparison of ABI group with a normal-hearing controls group (n=7) showed that TVA activations were significantly enhanced among controls group. ABI allowed the transmission of sound stimuli to temporal brain regions but lacked transmitting the specific cues of the human voice to the TVA. Moreover, among groups, during silent condition, brain visual regions showed higher rCBF in ABI group, although temporal brain regions had higher rCBF in the controls group. ABI patients had consequently developed enhanced visual strategies to keep interacting with their environment.

Speech performance and sound localization in a complex noisy environment in bilaterally implanted adult patients.

OBJECTIVE: To evaluate speech performance, in quiet and noise, and localization ability in adult patients who had undergone bilateral and simultaneous implantation. STUDY DESIGN: Prospective multi-center study. METHODS: Twenty-seven adult patients with profound or total hearing loss were bilaterally implanted in a single-stage procedure, and simultaneously activated (Med-El, Combi 40/40+). Subjects were assessed before implantation and at 3, 6 and 12 months after switch-on. Speech perception tests in monaural and binaural conditions were performed in quiet and in noise using disyllabic words, with speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Sound localization measurements were also performed in background noise coming from 5 loudspeakers positioned from -90 degrees to +90 degrees azimuth in the horizontal plane, and using a speech stimulus. RESULTS: There was a bilateral advantage at 12 months in quiet (77 +/- 5.0% in bilateral condition, 67 +/- 5.3% for the better ear, p < 0.005) and in noise (signal-to-noise ratio +15 dB: 63 +/- 5.9% in bilateral condition, 55 +/- 6.9% for the better ear, p < 0.05). Considering unilateral speech scores recorded in quiet at 12 months, subjects were categorized as 'good performers' (speech comprehension score > or =60% for the better ear, n = 19) and 'poor performers' (n = 8). Subjects were also categorized as 'asymmetrical' (difference between their 2 unilateral speech scores > or =20%, n = 11) or 'symmetrical' (n = 16). The largest advantage (bilateral compared to the better ear) was obtained in poor performers: +19% compared to +7% in good performers (p < 0.05). In the group of good performers, there was a bilateral advantage only in cases of symmetrical results between the 2 ears (n = 10). In the group of poor performers, the bilateral advantage was shown in both patients with symmetrical (n = 6) and asymmetrical results (n = 2). In bilateral conditions, the sound localization ability in noise was improved compared to monaural conditions in patients with symmetrical and asymmetrical performance between the 2 ears. No preoperative factor (age, duration of deafness, use of hearing aids, etiology, etc.) could predict the asymmetrical performance, nor which ear would be the best. CONCLUSION: This study demonstrates a bilateral advantage (at 12 months after the implantation) in speech intelligibility and sound localization in a complex noisy environment. In quiet, this bilateral advantage is shown in cases of poor performance of both ears, and in cases of good performance with symmetrical results between the 2 ears. No preoperative factor can predict the best candidates for a simultaneous bilateral implantation.

[Hearing loss among handicapped persons]. / La surdité parmi les handicaps.

Deafness appears to have a various impact on daily life, depending on the severity of the hearing loss. More often, mild and medium hearing loss are quickly rehabilited with hearing aids. Severe and profound hearing losses require a multidisciplinary evaluation, to determine the best treatment (speech therapy, cochlear implantation). Audiologic evaluation can be completed by handicap inventory specific for hearing loss, in order to appreciate the individual impact. Recently in France (2005) a law has demonstrated the determination of State's institutions to improve the daily life with handicap, and particularly in case of deafness.

Oral mobility reflects rate of progression in advanced Friedreich's ataxia.

Our objective was to identify a sensitive marker of disease progression in Friedreich's ataxia. We prospectively evaluated speech, voice, and oromotor function in 40 patients at two timepoints. The mean disease duration was 20.8 ± 9.8 years and mean SARA score 23.7 ± 8.6 at baseline. Oral motor mobility, assessed by a combination of movements of the face, eyes, cheeks, lips, and tongue, decreased significantly after 1 year (P < 0.0001). The standardized response mean over 12 months was considered as large for oral mobility (1.26) but small for SARA (0.12). Oral mobility could therefore be a sensitive marker in therapeutic trials.

Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice activations.

UNLABELLED: Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. METHODS: A PET H(2)(15)O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the "Lafon monosyllabic task" >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. RESULTS: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. CONCLUSION: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.

Diode laser in otosclerosis surgery: first clinical results.

OBJECTIVE: To evaluate the functional results of otosclerosis surgery using diode laser. STUDY DESIGN: Retrospective cohort analysis. PATIENTS: One hundred seven patients operated on for otosclerosis with a diode laser (119 ears, all primary cases) and 141 patients operated on with a conventional technique (141 ears, all primary cases). Revision cases using the diode laser were also described. METHODS: Preoperative tomographic computed scan findings and intraoperative observations were collected. Pure-tone and vocal audiometry was performed preoperatively and postoperatively (at 3 mo and 1 yr). RESULTS: In the laser group, the air-bone gap was 29 +/- 0.8 dB (n= 112) preoperatively and 9 +/- 0.6 dB (n = 58) at 1 year. Air conduction was improved by 22 +/- 1.7 dB at 1 year (n = 58). In the conventional group, the air-bone gap was 32 +/- 0.9 dB (n=127) preoperatively and 10 +/- 0.6 dB (n = 127) at 1 year. Air conduction was improved by 25 +/- 1.1 dB (n = 127) at 1 year. No difference of hearing gain was observed between the 2 groups at 1 year. A decreased rate of footplate fracture was observed with the diode laser (3.6%) compared with the conventional technique (21.3%). CONCLUSION: Diode laser is a reliable and safe device for otosclerosis surgery. The functional results were similar to those reported in other series.

A survey of satisfaction and use among patients fitted with a BAHA.

We compared the indices of satisfaction and use among patients wearing an osseo-integrated prosthesis BAHA (bone anchored hearing aid) according to the indications: conductive or mixed hearing loss (CHL) and patients with single side deafness (SSD). The study was carried out among patients wearing a BAHA fitted in one of three French departments between November 2001 and November 2005. Each patient received a postal questionnaire relating to the ease of use and the daily utilization period of the prosthesis, as well as a satisfaction rating (from 1 to 10) evaluating improvement in quality of life, overall satisfaction, improvement in sound localization and satisfaction from the aesthetic point of view. In total, 170 out of 231 patients responded to the questionnaire (response rate of 73.5%). The average age at the time of fitting of the BAHA was 56 years (18-79 years). The SSD group was composed of 118 patients (69.4%): 92 following surgery for vestibular schwannoma, 2 following surgery for meningioma and 24 with "other" causes (e.g. idiopathic sudden deafness, sensori neural hearing loss complicating surgery of the middle ear). The CHL group was composed of 52 patients (30.5%): 44 patients with a chronic otitis and 8 with a malformation of the middle ear. The average duration of use of the prosthesis was 22 months (3-72 months). The average utilization period was higher than 8 h per day in 48.5% of cases. There was a significant difference between the two groups concerning the quality of life (p < 0.0001), general satisfaction (p < 0.0001) and sound localization (p < 0.01). There was no significant difference concerning aesthetics. Among the patients of the CHL group, the levels of satisfaction and quality of life are comparable with recent data in the literature with scores of good or very good. The BAHA thus remains one of the methods of choice for hearing rehabilitation in this group of patients. Among the patients of the SSD group, the levels of satisfaction and quality of life are significantly poorer than in the CHL group, but remain generally good with the exception of sound localization. The treatment of SSD patients with a BAHA is interesting. A study comparing the BAHA with the WIFI CROS system is justified in order to ascertain the respective advantages of these two treatment options.

Fluctuating Hearing Loss in the Only Hearing Ear: Cochlear Implantation in the Contralateral Deaf Side.

Objective To investigate the hearing performance of adult patients presenting unilateral deafness with contralateral fluctuating hearing loss who received a cochlear implant on the deaf side. Study Design Case series with chart review. Setting University tertiary referral center. Subjects and Methods Preoperatively and at 6 and 12 months postoperatively, 23 patients underwent pure tone audiometry and speech audiometry with disyllabic and monosyllabic words in a quiet environment and sentences in quiet and noisy (signal-to-noise ratio +10 dB SPL) environments under best-aided conditions. The Abbreviated Profile of Hearing Aid Benefit (APHAB) inventory was evaluated preoperatively and at 6 and 12 months postoperatively. Results No difference was found between pre- and postoperative tests for disyllabic and monosyllabic words. For sentences in quiet and noisy environments, a difference between pre- and postoperative performance was present at 1 year ( P = .002 and P = .02, respectively). In a noisy environment, a difference was present at 6 and 12 months postoperatively as compared with the preoperative value (mean ± SD: 6 months: 42% ± 7.1% vs 61% ± 6.5%, P = .016). A significant improvement in the APHAB score was found at 6 and 12 months postimplantation (Friedman's 2-way analysis of variance by ranks, P < .001). The number of years of hearing deprivation of the deaf ear was not correlated with performance. Conclusion When incapacitating fluctuating hearing loss occurs in patients presenting a contralateral deaf ear, a cochlear implant is indicated in the latter ear, significantly improving performance in noisy conditions and allowing a better quality of communication to be achieved.

Evaluation of the management of postoperative aseptic meningitis.

BACKGROUND: A consensus conference recommended empirical antibiotic therapy for all patients with postoperative meningitis and treatment withdrawal after 48 or 72 h if cerebrospinal fluid culture results are negative. However, this approach is not universally accepted and has not been assessed in clinical trials. METHODS: We performed a cohort study of all patients who received a diagnosis of postoperative meningitis from January 1998 through May 2005 in a teaching hospital. From January 1998 through September 2003 (control period), guidelines were lacking or were not implemented. From October 2003 through May 2005 (interventional period), all patients received a predefined intravenous antibiotic therapy that was discontinued on the third day if the meningitis was considered aseptic. Clinical outcome and duration of antibiotic therapy were analyzed for each patient. RESULTS: Seventy-five episodes of postoperative meningitis (21 cases of bacterial meningitis and 54 cases of aseptic meningitis) were investigated. Patients with aseptic meningitis received antibiotic treatment for a mean +/- standard deviation duration of 11+/-5 days during the control period and 3.5+/-2 days during the intervention period (P=.001). The duration of antibiotic treatment for bacterial meningitis was not significantly different between the 2 periods. All episodes of bacterial and aseptic meningitis were cured, and complications were rare during both periods. CONCLUSIONS: Stopping antibiotic treatment after 3 days is effective and safe for patients with postoperative meningitis whose cerebrospinal fluid culture results are negative.